Oleic acid from cancer-associated fibroblast promotes cancer cell stemness by stearoyl-CoA desaturase under glucose-deficient condition

Background Cancer-associated fibroblasts (CAFs) coordinate the malignancy of cancer cells via secretory materials. Reprogrammed lipid metabolism and signaling play critical roles in cancer biology. Oleic acid (OA) serves as a source of energy under glucose-deficient conditions, but its function in cancer progression remains unclear. The present study investigated that CAFs in xenografted tumors had higher amounts of fatty acids, particularly OA, compared to normal fibroblasts, and promoted the cancer cell stemness in lung adenocarcinoma cells under glucose-deficient condition. Methods Xenografts were established in immunodeficient mice by injection of NCI-H460 (H460) cells. Lipids and fatty acids were evaluated using the BODIPY staining and fatty-acid methyl esters analysis. The expression levels of markers for lipid metabolism and cancer stemness were determined by western blot, flow cytometry, and real-time PCR. Cancer cell subclones against stearoyl-CoA desaturase (SCD) were produced by lentiviral vector and CRISPR/cas9 systems. The expression of SCD was examined immunochemically in human adenocarcinoma tissues, and its clinical relevance to survival rate in lung adenocarcinoma patients was assessed by Kaplan–Meier analysis. Results Transferred CAF-derived OA through lipid transporter upregulated SCD in cancer cells under glucose-deficient conditions, resulting in enhanced lipid metabolism and autophagosome maturation. By OA treatment under glucose deficient condition, cancer cell stemness was significantly enhanced through sequential activation of SCD, F-actin polymerization and nuclear translocation of yes-associated protein. These findings were confirmed by experiments using chemical inhibitors, SCD-overexpressing cells and SCD-knockout (KO) cells. When xenografted, SCD-overexpressing cells produced larger tumors compared with parental cells, while SCD-KO cells generated much smaller tumors. Analysis of tumor tissue microarray from lung adenocarcinoma patients revealed that SCD expression was the marker for poor prognosis involving tumor grade, clinical stage and survival rate. Conclusion Our data indicate that CAFs-derived OA activated lipid metabolism in lung adenocarcinoma cells under glucose-deficient conditions, subsequently enhancing stemness and progression toward malignancy.This study was supported by Basic Science Research Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education, Science and Technology (Grant Number: 2020R1A2C1010215) and the Brain Korea 21 future Veterinary Medicine Leading Education and Research Center, Research Institute of Veterinary Sciences, College of Veterinary Medicine, Seoul National University

Ovalicin attenuates atopic dermatitis symptoms by inhibiting IL-31 signaling and intracellular calcium influx

Atopic dermatitis (AD) is a common skin disorder difficult to be treated with medication. This study investigated the potential of ovalicin extracted from Cordyceps militaris for the treatment of AD using in vitro and in vivo models. We found that, in canine macrophage cell line DH82, lipopolysaccharide (LPS) upregulated the expression of genes associated with inflammation and pruritic responses through activating calcium and interleukin-31 (IL-31) signaling, and the upregulation could be suppressed by ovalicin, with an effect significantly stronger than dexamethasone. Ovalicin also reduced the expression of IL-31 downstream genes, including JAK2 (Janus kinase 2), TRPV1 (transient receptor potential vanilloid receptor-1), and HRH2 (histamine receptor H2). Ovalicin significantly alleviated the allergic symptoms in the AD mouse model. Histologically, the number of macrophages and mast cells infiltrated in the dermis was significantly reduced by ovalicin treatment. In the skin tissue of AD mice, reduction of IL-31 receptor was observed in the ovalicin treated group compared to the group without ovalicin treatment. To our knowledge, this is the first study to elucidate the anti-atopic mechanism of ovalicin, which could be an alternative to steroidal drugs commonly used for AD treatment.N

Three-dimensional artificial chirality towards low-cost and ultra-sensitive enantioselective sensing

Artificial chiral structures have potential applications in the field of enantioselective signal sensing. Advanced nanofabrication methods enable a large diversity in geometric structures and broad selectivity of materials, which can be exploited to manufacture artificial three-dimensional chiral structures. Various chiroptical phenomena exploiting spin and orbital angular momentum at the nanoscale have been continuously exploited as a way to effectively detect enantiomers. This review introduces precisely controlled bottom-up and large-area top-down metamaterial fabrication methods to solve the limitations of high manufacturing cost and low production speed. Particle synthesis, self-assembly, glanced angled vapor deposition, and three-dimensional plasmonic nanostructure printing are introduced. Furthermore, emerging sensitive chiral sensing methods such as cavity-enhanced chirality, photothermal circular dichroism, and helical dichroism of single particles are discussed. The continuous progress of nanofabrication technology presents the strong potential for developing artificial chiral structures for applications in biomedical, pharmaceutical, nanophotonic systems.11Nsciescopu

Clinical utility of immature reticulocyte fraction for identifying early red blood cell regeneration in anemic dogs

Abstract Background Evaluating regeneration is essential for the classification and differential diagnosis of anemia in dogs. Early detection of regeneration is challenging in anemic dogs. Objectives This study assessed the value of immature reticulocyte fraction (IRF) in differentiating preregenerative anemia (PRA) from nonregenerative anemia (NRA) in dogs. Animals Ninety‐four dogs: 49 controls and 45 with anemia. Methods Case‐control study. Fractions of low‐, medium‐ (MFR), and high‐fluorescence reticulocytes (HFR), were measured using the ADVIA 2120i hematology analyzer. The IRF was calculated as the sum of percentages of MFR and HFR. Data from dogs with regenerative anemia (RA, n = 19), PRA (n = 11), and NRA (n = 15) were retrospectively analyzed. The value of IRF was compared with reticulocyte production index (RPI) using the receiver operating characteristic (ROC) curve. Results The median of IRF was significantly higher in dogs with RA (46.5%; range, 40.9‐53.6%; P  .99) but was higher than dogs with NRA (18.7%; range, 8.8‐24%; P = .00). The area under the ROC curve of IRF was superior to that of RPI (0.897 vs 0.818, P = .00) in differentiating dogs with PRA from NRA. Conclusions and Clinical Importance The IRF is a reliable variable for detecting early regeneration in anemic dogs without reticulocytosis. The study suggests that the measurement of IRF could be useful in classifying anemic dogs

Reduction in mitochondrial oxidative stress mediates hypoxia-induced resistance to cisplatin in human transitional cell carcinoma cells

Tumor hypoxia is known to promote the acquisition of more aggressive phenotypes in human transitional cell carcinoma (TCC), including drug resistance. Accumulating evidence suggests that mitochondria play a central role in the chemoresistance of TCC. However, the role of mitochondria in the hypoxia-induced drug resistance in TCC remains elusive. The present study investigated the function of mitochondria in the drug resistance using a TCC cell line under hypoxic conditions. In vitro hypoxia (0.1% O2, 48 h) was achieved by incubating TCC cells in air chamber. Mitochondrial events involving hypoxia-induced drug resistance were assessed. Hypoxia significantly reduced the cisplatin-induced apoptosis of TCC cells. Additionally, hypoxia substantially decreased the level of mitochondrial reactive oxygen species (ROS) generated by cisplatin treatment. Analogously, elimination of mitochondrial ROS significantly rescued cells from cisplatin-induced apoptosis. Hypoxia enhanced mitochondrial hyperpolarization, which was not related to ATP production or the reversal of ATP synthase activity. The mitochondrial DNA (mtDNA) amplification efficiency data illustrated that hypoxia significantly prevented oxidative damage to the mitogenome. Moreover, transmission electron microscopy revealed that cisplatin-induced disruption of the mitochondrial ultrastructure was abated under hypoxic conditions. Notably, depletion of mtDNA by ethidium bromide abrogated hypoxia-induced resistance to cisplatin. Taken together, the present study demonstrated that TCC cells exposed to hypoxic conditions rendered mitochondria less sensitive to oxidative stress induced by cisplatin treatment, leading to enhanced drug resistance

Tunable one-step nanoimprinted RGB-achromatic bifocal metalens

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Atypical antibiotic-responsive Staphylococcus pseudintermedius-associated tumor-like meibomitis in the upper eyelid: A case report of two dogs

ObjectiveTo present the clinical signs and treatment methods for atypical tumor-like meibomitis in two dogs. Animals StudiedA 4-year-old castrated-male Coton de Tulear (Case 1) and a 6-year-old spayed-female Maltese dog (Case 2). ProcedureFull ophthalmic examination revealed a well-circumscribed, firm, and raised solitary mass on the upper eyelid of the left (Case 1) and right eye (Case 2). Case 1 showed a recurrent mass with a diameter of 2-3 mm, which was excised by the referring veterinarian. The possibility of meibomian gland involvement was suggested histopathologically. Case 2 had a history of blepharitis treated with systemic corticosteroids 4 years ago. ResultsTopical and systemic antibiotics and anti-inflammatory drugs were administered to reduce inflammation and prevent secondary infections. In Case 1, the mass appeared static at the beginning of medication; however, after stopping antibiotics while tapering steroids, the mass increased in size and was associated with suppurative discharge. In Case 2, the mass continued to grow despite treatment, showing a similar infection pattern. Cytological examination revealed neutrophilic inflammation with cocci infection, and bacterial culture confirmed the presence of Staphylococcus pseudintermedius in both cases. When steroid administration was stopped and antibiotic administration was initiated according to the results of the antibiotic susceptibility test, the mass rapidly decreased in size and completely disappeared. There was no recurrence on follow-up. ConclusionsA unilateral antibiotic-responsive tumor-like solitary mass on the upper eyelid resolved without surgical treatment. Medical treatment must be considered when treating atypical eyelid masses, and the use of appropriate antibiotics through antibiotic susceptibility testing is important.N

Hypoxia promotes acquisition of aggressive phenotypes in human malignant mesothelioma

Abstract Background Hypoxia is a hallmark of the solid tumor microenvironment and is associated with poor outcomes in cancer patients. The present study was performed to investigate mechanisms underlying the hypoxia-induced phenotypic changes using human malignant mesothelioma (HMM) cells. Methods Hypoxic conditions were achieved by incubating HMM cells in the air chamber. The effect of hypoxia on phenotype changes in HMM cells was investigated by performing in vitro clonogenicity, drug resistance, migration, and invasion assays. Signaling pathways and molecules involved in the more aggressive behaviors of HMM cells under hypoxia were investigated. A two-tailed unpaired Student’s t-test or one-way ANOVA with Bonferroni post-test correction was used in this study. Results Hypoxic conditions upregulated hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α in parallel with the upregulation of its target, Glut-1, in HMM cells. In vitro clonogenicity of HMM cells was significantly increased in hypoxic conditions, but the proliferation of cells at a high density in hypoxia was lower than that in normoxic conditions. The expression levels of HIF-2α and Oct4 were increased in hypoxic HMM cells. The percentage of cells with high CD44 expression was significantly higher in HMM cells cultured in hypoxia than those cultured in normoxia. Hypoxia significantly enhanced the resistance of HMM cells to cisplatin, which occurred through cytoprotection against cisplatin-induced apoptosis. While cisplatin treatment decreased the ratio of Bcl-2 to Bax in normoxic condition, hypoxia conversely increased the ratio in HMM cells treated with cisplatin. Hypoxia increased the mobility and invasiveness of HMM cells. Epithelial to mesenchymal transition was promoted, which was indicated by the repression of E-cadherin and the concomitant increase of vimentin in HMM cells. Conclusions The data illustrated that hypoxic conditions augmented the aggressive phenotypes of HMM cells at the biological and molecular levels. The present study provides valuable background information beginning to understand aggressiveness of HMM in tumor microenvironments, suggesting that a control measure for tumor hypoxia may be an effective therapeutic strategy to reduce the aggressiveness of cancer cells in HMM patients

Subungual Pigmented Squamous Cell Carcinoma in a Dog

© 2022 Elsevier LtdAn 11-year-old spayed female Miniature Schnauzer dog was presented with loss of a claw caused by a nail bed mass. Histopathological evaluation revealed that the mass comprised neoplastic squamous cells with abundant cytoplasmic melanin pigment. Immunohistochemically, the neoplastic cells were positive for cytokeratin and negative for vimentin and ionized calcium-binding adaptor molecule 1, supporting a diagnosis of pigmented squamous cell carcinoma. To our knowledge, this is the first report of subungual pigmented squamous cell carcinoma in animals.N

Single-Metal-Atom Dopants Increase the Lewis Acidity of Metal Oxides and Promote Nitrogen Fixation

© 2021 American Chemical Society.Exploring Earth-abundant metal oxides for ambient N2 (Lewis base) reduction to value-added NH3, an essential commodity for modern industries, has extreme significance. However, due to their insufficient Lewis acidity and unfavorable electronic parameters, resulting in poor N2 adsorption, instability of key N intermediates (NNH*/NNH2*/N*), and preference for hydrogen evolution, the NH3 selectivity and yield rate with metal oxides are far from satisfactory. Herein, theoretical predictions reveal that tuning the electronic structure of defective Co3O4 (Co3O4-x) via a single-Ru-atom dopant can cooperatively enhance the N2 adsorption, driven by strong Ru4d-N2p orbital coupling, and stabilize the key N-intermediates, further suppressing the H∗ dimerization and significantly boosting the NH3 selectivity. Motivated by DFT predictions, we introduced optimal single-Ru-atom dopants to maximize the Lewis acidity of Co3O4 with in situ-generated oxygen defects (Ru1.4Co3O4-x), which exhibited an excellent N2-fixation activity with a high NH3 Faradaic efficiency (40.2%) and yield rate (39.4 μg/h/mgcat; 2.67 mg/h/mgRu) at 0 V (vs RHE), along with long-term stability and 2.5 times higher selectivity than pristine Co3O4-x, outperforming the state-of-the-art Ru/C.11Nsciescopu