CD109 Attenuates Bleomycin-induced Pulmonary Fibrosis by Inhibiting TGF-ß Signaling.

Pulmonary fibrosis is a fatal condition characterized by fibroblast and myofibroblast proliferation and collagen deposition. TGF-ß plays a pivotal role in the development of pulmonary fibrosis. Therefore, modulation of TGF-ß signaling is a promising therapeutic strategy for treating pulmonary fibrosis. To date, however, interventions targeting TGF-ß have not shown consistent efficacy. CD109 is a GPI-anchored glycoprotein that binds to TGF-ß receptor I and negatively regulates TGF-ß signaling. However, no studies have examined the role and therapeutic potential of CD109 in pulmonary fibrosis. The purpose of this study was to determine the role and therapeutic value of CD109 in bleomycin-induced pulmonary fibrosis. CD109-transgenic mice overexpressing CD109 exhibited significantly attenuated pulmonary fibrosis, preserved lung function, and reduced lung fibroblasts and myofibroblasts compared with wild-type (WT) mice. CD109-/- mice exhibited pulmonary fibrosis comparable to WT mice. CD109 expression was induced in variety types of cells, including lung fibroblasts and macrophages, upon bleomycin exposure. Recombinant CD109 protein inhibited TGF-ß signaling and significantly decreased ACTA2 expression in human fetal lung fibroblast cells in vitro. Administration of recombinant CD109 protein markedly reduced pulmonary fibrosis in bleomycin-treated WT mice in vivo. Our results suggest that CD109 is not essential for the development of pulmonary fibrosis, but excess CD109 protein can inhibit pulmonary fibrosis development, possibly through suppression of TGF-ß signaling. CD109 is a novel therapeutic candidate for treating pulmonary fibrosis.

Accelerated Water Desorption of Oligomeric Poly(ethylene glycol) by Addition of Poly(propylene glycol) for Energy-Efficient Water Recovery Systems.

Adsorbents are used to recover water vapor from the atmosphere in desiccant air conditioning (DAC) and atmospheric water harvesting (AWH) systems. Solid adsorbents have been conventionally used in these systems, though liquid adsorbents are considered to be more effective for energy-efficient fluidic thermosystems because of their low regeneration temperatures (45-70 °C). While most previous studies have focused on improving the adsorption performance, the desorption performance of adsorbents can also be a critical factor in improving the energy efficiency of these systems. Thus, this study aimed to improve the water desorption efficiency, focusing on the liquid adsorbents. We found that mixing hydrophobic molecules into a liquid adsorbent decreases the desorption temperature and increases the water-desorption efficiency. Oligomeric poly(ethylene glycol) (PEG), a common moisture-adsorbing liquid oligomer used in detergents and cosmetics, was selected as the liquid adsorbent. Oligomeric poly(propylene glycol) (PPG), which has a structure analogous to PEG and lower hygroscopicity, was selected as the hydrophobic molecule. Water adsorption and desorption experiments showed that the mixture of PPG with PEG promoted the desorption of water molecules beyond that of PEG, while thermogravimetric differential thermal analysis revealed a decrease in the water desorption temperature with increasing PPG content. The improved desorption efficiency was ascribed to the likely water adsorption equilibrium between PEG and PPG in the blend; water molecules are preferentially desorbed from PPG, which has weaker water-adsorbate interactions. The proposed concept is expected to be incorporated into various hygroscopic liquids to develop energy-efficient liquid adsorbents for DAC and AWH.

Meflin is a marker of pancreatic stellate cells involved in fibrosis and epithelial regeneration in the pancreas.

Pancreatic stellate cells (PSCs) are stromal cells in the pancreas that play an important role in pancreatic pathology. In chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC), PSCs are known to get activated to form myofibroblasts or cancer-associated fibroblasts (CAFs) that promote stromal fibroinflammatory reactions. However, previous studies on PSCs were mainly based on the findings obtained using ex vivo expanded PSCs, with few studies that addressed the significance of in situ tissue-resident PSCs using animal models. Their contributions to fibrotic reactions in CP and PDAC are also lesser-known. These limitations in our understanding of PSC biology have been attributed to the lack of specific molecular markers of PSCs. Herein, we established Meflin (Islr), a glycosylphosphatidylinositol-anchored membrane protein, as a PSC-specific marker in both mouse and human by using human pancreatic tissue samples and Meflin reporter mice. Meflin-positive (Meflin+ ) cells contain lipid droplets and express the conventional PSC marker Desmin in normal mouse pancreas, with some cells also positive for Gli1, the marker of pancreatic tissue-resident fibroblasts. Three-dimensional analysis of the cleared pancreas of Meflin reporter mice showed that Meflin+ PSCs have long and thin cytoplasmic protrusions, and are localised on the abluminal side of vessels in the normal pancreas. Lineage tracing experiments revealed that Meflin+ PSCs constitute one of the origins of fibroblasts and CAFs in CP and PDAC, respectively. In these diseases, Meflin+ PSC-derived fibroblasts showed a distinctive morphology and distribution from Meflin+ PSCs in the normal pancreas. Furthermore, we showed that the genetic depletion of Meflin+ PSCs accelerated fibrosis and attenuated epithelial regeneration and stromal R-spondin 3 expression, thereby implying that Meflin+ PSCs and their lineage cells may support tissue recovery and Wnt/R-spondin signalling after pancreatic injury and PDAC development. Together, these data indicate that Meflin may be a marker specific to tissue-resident PSCs and useful for studying their biology in both health and disease. © 2023 The Pathological Society of Great Britain and Ireland.

Significance of expression of CD109 in osteosarcoma and its involvement in tumor progression via BMP signaling.

Osteosarcoma, the most common primary malignant bone tumor, is defined by the formation of neoplastic osteoid and/or bone. This sarcoma is a highly heterogeneous disease with a wide range of patient outcomes. CD109 is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed in various types of malignant tumors. We previously reported that CD109 is expressed in osteoblasts and osteoclasts in normal human tissues and plays a role in bone metabolism in vivo. While CD109 has been shown to promote various carcinomas through the downregulation of TGF-ß signaling, the role and mechanism of CD109 in sarcomas remain largely unknown. In this study, we investigated the molecular function of CD109 in sarcomas using osteosarcoma cell lines and tissue. Semi-quantitative immunohistochemical analysis using human osteosarcoma tissue revealed a significantly worse prognosis in the CD109-high group compared with the CD109-low group. We found no association between CD109 expression and TGF-ß signaling in osteosarcoma cells. However, enhancement of SMAD1/5/9 phosphorylation was observed in CD109 knockdown cells under bone morphogenetic protein-2 (BMP-2) stimulation. We also performed immunohistochemical analysis for phospho-SMAD1/5/9 using human osteosarcoma tissue and found a negative correlation between CD109 expression and SMAD1/5/9 phosphorylation. In vitro wound healing assay showed that osteosarcoma cell migration was significantly attenuated in CD109-knockdown cells compared with control cells in the presence of BMP. These results suggest that CD109 is a poor prognostic factor in osteosarcoma and affects tumor cell migration via BMP signaling.

Polarization-dependent plasmonic heating in epitaxially grown multilayered metal-organic framework thin films embedded with Ag nanoparticles.

The development of metal-organic framework (MOF) thin films with various functionalities has paved the way for research into a wide variety of applications. MOF-oriented thin films can exhibit anisotropic functionality in the not only out-of-plane but also in-plane directions, making it possible to utilize MOF thin films for more sophisticated applications. However, the functionality of oriented MOF thin films has not been fully exploited, and finding novel anisotropic functionality in oriented MOF thin films should be cultivated. In the present study, we report the first demonstration of polarization-dependent plasmonic heating in a MOF oriented film embedded with Ag nanoparticles (AgNPs), pioneering an anisotropic optical functionality in MOF thin films. Spherical AgNPs exhibit polarization-dependent plasmon-resonance absorption (anisotropic plasmon damping) when incorporated into an anisotropic lattice of MOFs. The anisotropic plasmon resonance results in a polarization-dependent plasmonic heating behavior; the highest elevated temperature was observed in case the polarization of incident light is parallel to the crystallographic axis of the host MOF lattice favorable for the larger plasmon resonance, resulting in polarization-controlled temperature regulation. Such spatially and polarization selective plasmonic heating offered by the use of oriented MOF thin films as a host can pave the way for applications such as efficient reactivation in MOF thin film sensors, partial catalytic reactions in MOF thin film devices, and soft microrobotics in composites with thermo-responsive materials.

CD109 on Dendritic Cells Regulates Airway Hyperreactivity and Eosinophilic Airway Inflammation.

Asthma is a chronic airway inflammatory disease characterized by airway hyperreactivity (AHR) and eosinophilic airway inflammation. Dendritic cells (DCs) are essential for the development of asthma via presenting allergens, causing T-helper cell type 2 (Th2) skewing and eosinophil inflammation. Recent studies have revealed that CD109, a glycosylphosphatidylinositol-anchored glycoprotein, is involved in the pathogenesis of inflammatory diseases such as rheumatoid arthritis and psoriasis. However, no study has addressed the role of CD109 in asthma. This study sought to address the role of CD109 on DCs in the development of AHR and allergic inflammation. CD109-deficient mice (CD109-/-) were sensitized with house dust mite or ovalbumin and compared with wild-type mice for induction of AHR and allergic inflammation. CD109-deficient mice had reduced AHR and eosinophilic inflammation together with lower Th2 cytokine expression compared with wild-type mice. Interestingly, CD109 expression was induced in lung conventional DC2s (cDC2s), but not lung cDC1s, upon allergic challenge. Lung cDC2s from CD109-/- mice had a poor ability to induce cytokine production in ex vivo DC-T cell cocultures with high expression of RUNX3 (runt-related transcription factor 3), resulting in suppression of Th2 differentiation. Adoptive transfer of bone marrow-derived CD109-/- DCs loaded with house dust mite failed to develop AHR and eosinophilic inflammation. Finally, administration of monoclonal anti-CD109 antibody reduced airway eosinophils and significantly decreased AHR. Our results suggest the involvement of CD109 in asthma pathogenesis. CD109 is a novel therapeutic target for asthma.

Girdin Promotes Tumorigenesis and Chemoresistance in Lung Adenocarcinoma by Interacting with PKM2.

Girdin, an Akt substrate, has been reported to promote tumorigenesis in various tumors. However, the role of Girdin in a spontaneous tumor model has not yet been explored. Here, we studied the role of Girdin in lung adenocarcinoma (LUAD) using the autochthonous mouse model and found that Girdin led to LUAD progression and chemoresistance by enhancing the Warburg effect. Mechanistically, Girdin interacted with pyruvate kinase M2 (PKM2), which played a vital role in aerobic glycolysis. Furthermore, Girdin impaired Platelet Derived Growth Factor Receptor Beta (PDGFRß) degradation, which in turn, promoted PKM2 tyrosine residue 105 (Y105) phosphorylation and inhibited PKM2 activity, subsequently promoting aerobic glycolysis in cancer cells. Taken together, our study demonstrates that Girdin is a crucial regulator of tumor growth and may be a potential therapeutic target for overcoming the resistance of LUAD cells to chemotherapy.

Pharmacologic conversion of cancer-associated fibroblasts from a protumor phenotype to an antitumor phenotype improves the sensitivity of pancreatic cancer to chemotherapeutics.

Previous therapeutic attempts to deplete cancer-associated fibroblasts (CAFs) or inhibit their proliferation in pancreatic ductal adenocarcinoma (PDAC) were not successful in mice or patients. Thus, CAFs may be tumor suppressive or heterogeneous, with distinct cancer-restraining and -promoting CAFs (rCAFs and pCAFs, respectively). Here, we showed that induced expression of the glycosylphosphatidylinositol-anchored protein Meflin, a rCAF-specific marker, in CAFs by genetic and pharmacological approaches improved the chemosensitivity of mouse PDAC. A chemical library screen identified Am80, a synthetic, nonnatural retinoid, as a reagent that effectively induced Meflin expression in CAFs. Am80 administration improved the sensitivity of PDAC to chemotherapeutics, accompanied by increases in tumor vessel area and intratumoral drug delivery. Mechanistically, Meflin was involved in the suppression of tissue stiffening by interacting with lysyl oxidase to inhibit its collagen crosslinking activity. These data suggested that modulation of CAF heterogeneity may represent a strategy for PDAC treatment.

Guest Alignment and Defect Formation during Pore Filling in Metal-Organic Framework Films.

The degree of pore filling is an important parameter for defining guest@MOF properties in applications including electronics, optics, and gas separation. However, the interplay of key aspects of host-guest interactions, such as a quantitative description of the guest alignment or the structural integrity of the host as function of pore filling are yet to be determined. Polarisation-dependent infrared spectroscopy in attenuated total reflection configuration combined with gas sorption allowed to simultaneously study the orientation of the guest molecule and structural changes of the MOF framework during the pore filling process. Thereby we found, that initially randomly oriented guest molecules align with increasing pore filling during adsorption from the gas phase. At the same time, the framework itself undergoes a reversible, guest molecule-dependent rotation of the aromatic linker and a linker detachment process, which induce defects.

Hyperopia-Correcting Phototherapeutic Keratectomy and Its Comparison With Conventional Phototherapeutic Keratectomy.

Purpose: To evaluate hyperopia-correcting phototherapeutic keratectomy (HC-PTK) and to compare the visual and refractive outcomes of HC-PTK and conventional PTK. Methods: This study comprised a total of 72 eyes of 72 consecutive patients who underwent HC-PTK and conventional PTK for granular corneal dystrophy or band-shaped keratopathy. Preoperatively and 6 months postoperatively, we assessed visual acuity, manifest refraction, and mean keratometry, as well as postoperative corneal higher-order aberrations and adverse events in each PTK group, and compared these metrics between the two groups. Results: LogMAR BSCVA significantly improved from 0.43 ± 0.47 preoperatively to 0.21 ± 0.38 postoperatively in the HC-PTK group (Wilcoxon signed-rank test, p < 0.001). It was also significantly improved from 0.22 ± 0.21 preoperatively to 0.15 ± 0.12 postoperatively in the conventional PTK group (p = 0.031). Mean refraction significantly changed from 0.27 ± 1.55 diopter (D) preoperatively to 0.50 ± 1.77 D postoperatively, in the HC-PTK group (p = 0.313). By contrast, it was significantly hyperopic from -0.15 ± 2.41 D preoperatively to 1.45 ± 2.46 D postoperatively, in the conventional PTK group (p < 0.001). No significant complications occurred in any case during the follow-up period. Conclusion: Both HC-PTK and conventional PTK showed a significant improvement of BSCVA and no vision-threatening complications at any time in this series. HC-PTK significantly reduced a hyperopic shift in refraction compared with conventional PTK, suggesting its viability for patients requiring PTK, especially in consideration of preventing this hyperopic issue.

RET receptor signaling: Function in development, metabolic disease, and cancer.

The RET proto-oncogene encodes a receptor tyrosine kinase whose alterations are responsible for various human cancers and developmental disorders, including thyroid cancer, non-small cell lung cancer, multiple endocrine neoplasia type 2, and Hirschsprung's disease. RET receptors are physiologically activated by glial cell line-derived neurotrophic factor (GDNF) family ligands that bind to the coreceptor GDNF family receptor α (GFRα). Signaling via the GDNF/GFRα1/RET ternary complex plays crucial roles in the development of the enteric nervous system, kidneys, and urinary tract, as well as in the self-renewal of spermatogonial stem cells. In addition, another ligand, growth differentiation factor-15 (GDF15), has been shown to bind to GFRα-like and activate RET, regulating body weight. GDF15 is a stress response cytokine, and its elevated serum levels affect metabolism and anorexia-cachexia syndrome. Moreover, recent development of RET-specific kinase inhibitors contributed significantly to progress in the treatment of patients with RET-altered cancer. This review focuses on the broad roles of RET in development, metabolic diseases, and cancer.

Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade.

Cancer-associated fibroblasts (CAFs) are an integral component of the tumor microenvironment (TME). Most CAFs shape the TME toward an immunosuppressive milieu and attenuate the efficacy of immune checkpoint blockade (ICB) therapy. However, the detailed mechanism of how heterogeneous CAFs regulate tumor response to ICB therapy has not been defined. Here, we show that a recently defined CAF subset characterized by the expression of Meflin, a glycosylphosphatidylinositol-anchored protein marker of mesenchymal stromal/stem cells, is associated with survival and favorable therapeutic response to ICB monotherapy in patients with non-small cell lung cancer (NSCLC). The prevalence of Meflin-positive CAFs was positively correlated with CD4-positive T-cell infiltration and vascularization within non-small cell lung cancer tumors. Meflin deficiency and CAF-specific Meflin overexpression resulted in defective and enhanced ICB therapy responses in syngeneic tumors in mice, respectively. These findings suggest the presence of a CAF subset that promotes ICB therapy efficacy, which adds to our understanding of CAF functions and heterogeneity.

Clinical evaluation of flat peripheral curve design with aspherical-curve and multi-curve hard contact lenses for keratoconus.

Aspherical- and multi-curve rigid gas-permeable hard contact lenses (HCLs) have a flattened curve in the peripheral zone and are mostly used for patients with keratoconus who cannot wear glasses, soft contact lenses, or spherical HCLs. In this retrospective study, a total of 95 eyes of 77 patients who used aspherical- or multi-curve HCLs (mean age: 40.0 ± 11.0 years) were evaluated. This study examined the types of aspherical- and multi-curve HCLs, best-corrected visual acuity (BCVA) values before and after wearing HCLs, the association with the Amsler-Krumeich classification, duration of wear, corneal/conjunctival disorder, and the frequency of changing HCLs. There were 78 eyes that used aspherical-curve HCLs and 17 that used multi-curve HCLs. BCVA significantly improved from 0.42 logMAR to 0.06 logMAR after wearing either form of HCL. The Amsler-Krumeich classification showed that aspherical-curve HCLs were commonly used for patients with stage 2 keratoconus, and multi-curve HCLs were commonly used for stage 4 patients. The BCVA values were worse when the disease stage was more severe (stages 3 and 4) regardless of HCL type. The mean base curve of the lenses was steeper in multi-curve HCLs than in aspherical-curve HCLs. The more severe the disease stage, the steeper the base curve in both aspherical- and multi-curve HCLs. The duration of wear significantly improved from 2.1 h to 10.2 h, and corneal/conjunctival disorder similarly improved. The mean frequency of changing HCL types was 1.1 times. This study suggests that a flat peripheral curve design with aspherical- and multi-curve HCLs is useful for patients with keratoconus.

Matrix remodeling-associated protein 8 is a marker of a subset of cancer-associated fibroblasts in pancreatic cancer.

Cancer-associated fibroblasts (CAFs), a compartment of the tumor microenvironment, were previously thought to be a uniform cell population that promotes cancer progression. However, recent studies have shown that CAFs are heterogeneous and that there are at least two types of CAFs, that is, cancer-promoting and -restraining CAFs. We previously identified Meflin as a candidate marker of cancer-restraining CAFs (rCAFs) in pancreatic ductal adenocarcinoma (PDAC). The precise nature of rCAFs, however, has remained elusive owing to a lack of understanding of their comprehensive gene signatures. Here, we screened genes whose expression correlated with Meflin in single-cell transcriptomic analyses of human cancers. Among the identified genes, we identified matrix remodeling-associated protein 8 (MXRA8), which encodes a type I transmembrane protein with unknown molecular function. Analysis of MXRA8 expression in human PDAC samples showed that MXRA8 was differentially co-expressed with other CAF markers. Moreover, in patients with PDAC or syngeneic tumors developed in MXRA8-knockout mice, MXRA8 expression did not affect the roles of CAFs in cancer progression, and the biological importance of MXRA8+ CAFs is still unclear. Overall, we identified MXRA8 as a new CAF marker; further studies are needed to determine the relevance of this marker.

CD109 expression in tumor cells and stroma correlates with progression and prognosis in pancreatic cancer.

CD109 is a glycosylphosphatidylinositol-anchored glycoprotein, whose expression is upregulated in some types of malignant tumors. High levels of CD109 in tumor cells have been reported to correlate with poor prognosis; however, significance of CD109 stromal expression in human malignancy has not been elucidated. In this study, we investigated the tumorigenic properties of CD109 in pancreatic ductal adenocarcinoma (PDAC). Immunohistochemical analysis of 92 PDAC surgical specimens revealed that positive CD109 expression in tumor cells was significantly associated with poor prognosis (disease-free survival, p = 0.003; overall survival, p = 0.002), and was an independent prognostic factor (disease-free survival, p = 0.0173; overall survival, p = 0.0104) in PDAC. Furthermore, CD109 expression was detected in the stroma surrounding tumor cells, similar to that of α-smooth muscle actin, a histological marker of cancer-associated fibroblasts. The stromal CD109 expression significantly correlated with tumor progression in PDAC (TNM stage, p = 0.033; N factor, p = 0.024; lymphatic invasion, p = 0.028). In addition, combined assessment of CD109 in tumor cells and stroma could identify the better prognosis group of patients from the entire patient population. In MIA PaCa-2 PDAC cell line, we demonstrated the involvement of CD109 in tumor cell motility, but not in PANC-1. Taken together, CD109 not only in the tumor cells but also in the stroma is involved in the progression and prognosis of PDAC, and may serve as a useful prognostic marker in PDAC.

The Origin and Contribution of Cancer-Associated Fibroblasts in Colorectal Carcinogenesis.

BACKGROUND & AIMS: Cancer-associated fibroblasts (CAFs) play an important role in colorectal cancer (CRC) progression and predict poor prognosis in CRC patients. However, the cellular origins of CAFs remain unknown, making it challenging to therapeutically target these cells. Here, we aimed to identify the origins and contribution of colorectal CAFs associated with poor prognosis. METHODS: To elucidate CAF origins, we used a colitis-associated CRC mouse model in 5 different fate-mapping mouse lines with 5-bromodeoxyuridine dosing. RNA sequencing of fluorescence-activated cell sorting-purified CRC CAFs was performed to identify a potential therapeutic target in CAFs. To examine the prognostic significance of the stromal target, CRC patient RNA sequencing data and tissue microarray were used. CRC organoids were injected into the colons of knockout mice to assess the mechanism by which the stromal gene contributes to colorectal tumorigenesis. RESULTS: Our lineage-tracing studies revealed that in CRC, many ACTA2+ CAFs emerge through proliferation from intestinal pericryptal leptin receptor (Lepr)+ cells. These Lepr-lineage CAFs, in turn, express melanoma cell adhesion molecule (MCAM), a CRC stroma-specific marker that we identified with the use of RNA sequencing. High MCAM expression induced by transforming growth factor ß was inversely associated with patient survival in human CRC. In mice, stromal Mcam knockout attenuated orthotopically injected colorectal tumoroid growth and improved survival through decreased tumor-associated macrophage recruitment. Mechanistically, fibroblast MCAM interacted with interleukin-1 receptor 1 to augment nuclear factor κB-IL34/CCL8 signaling that promotes macrophage chemotaxis. CONCLUSIONS: In colorectal carcinogenesis, pericryptal Lepr-lineage cells proliferate to generate MCAM+ CAFs that shape the tumor-promoting immune microenvironment. Preventing the expansion/differentiation of Lepr-lineage CAFs or inhibiting MCAM activity could be effective therapeutic approaches for CRC.

Effect of Platelet-Rich Plasma on Corneal Epithelial Healing after Phototherapeutic Keratectomy: An Intraindividual Contralateral Randomized Study.

PURPOSE: To assess the effect of platelet-rich plasma (PRP) on the healing response of the corneal epithelium in eyes undergoing phototherapeutic keratectomy (PTK). METHODS: We prospectively examined 20 eyes of 10 patients undergoing bilateral PTK for granular corneal dystrophy or band keratopathy. Patients were randomly assigned to start topical administration of PRP ophthalmic suspension (PRP group) or artificial tears (control group) 4 times daily for 2 weeks. Immediately, 1, and 2 days, and 1 week after PTK, we quantitatively measured the staining area of the corneal epithelium, using slit-lamp photography. We also determined the subjective symptoms and the satisfaction, using the visual analogue system (VAS). RESULTS: The staining area in the PRP group was significantly smaller than that in the control group on days 1 and 2 (Wilcoxon signed-rank test, p = 0.022 and p = 0.017, respectively), but not on day 7 (p = 0.317). The recovery rate of the corneal epithelium in the PRP group was significantly higher than that in the control group on days 1 and 2 (p = 0.022 and p = 0.017, respectively), but not on day 7 (p = 0.317). We found no significant differences in pain (p = 0.139), foreign body sensation (p = 0.108), epiphora (p = 1.000), or satisfaction (p = 0.295), between the two groups. Postoperative complications did not occur in any of the eyes in the study. CONCLUSIONS: The PRP treatment was effective for enhancing corneal epithelial recovery in the early postoperative period, without significant adverse events, in post-PTK-treated eyes, suggesting that it may hold promise as one of the treatment options for treating such postsurgical patients.

Roles of the Mesenchymal Stromal/Stem Cell Marker Meflin/Islr in Cancer Fibrosis.

Fibroblasts synthesise the extracellular matrix (ECM) such as collagen and elastin, the excessive accumulation of which can lead to fibrosis and organ dysfunction under pathological conditions. Cancer-associated fibroblasts (CAFs) are major constituents of the tumour microenvironment (TME) that accompany the desmoplastic reaction responsible for anti-cancer treatment resistance. Thus, it is important to dissect the roles of CAFs in the TME to develop new therapeutic strategies for refractory cancers. Recent progress in the studies of CAF biology suggests that the functions of CAFs are complicated and that they are composed of functionally distinct populations, including cancer-promoting CAFs (pCAFs) and cancer-restraining CAFs (rCAFs). We recently identified a new cell surface marker for rCAFs in pancreatic and colon cancers, designated as Meflin (mesenchymal stromal cell- and fibroblast-expressing Linx paralogue)/Islr (immunoglobulin super family containing leucine-rich repeat). Based on the distribution of Meflin/Islr-positive cells, we also considered it a specific candidate marker for mesenchymal stroma/stem cells. Meflin/Islr-positive CAFs have been shown to suppress cancer progression by being involved in regulating collagen structures and BMP signalling in the TME. This review describes the function of Meflin/Islr in cancer fibrosis as well as in cardiac and lung fibrosis and its potential in the development of new cancer therapeutics.

Daple deficiency causes hearing loss in adult mice by inducing defects in cochlear stereocilia and apical microtubules.

The V-shaped arrangement of hair bundles on cochlear hair cells is critical for auditory sensing. However, regulation of hair bundle arrangements has not been fully understood. Recently, defects in hair bundle arrangement were reported in postnatal Dishevelled-associating protein (ccdc88c, alias Daple)-deficient mice. In the present study, we found that adult Daple-/- mice exhibited hearing disturbances over a broad frequency range through auditory brainstem response testing. Consistently, distorted patterns of hair bundles were detected in almost all regions, more typically in the basal region of the cochlear duct. In adult Daple-/- mice, apical microtubules were irregularly aggregated, and the number of microtubules attached to plasma membranes was decreased. Similar phenotypes were manifested upon nocodazole treatment in a wild type cochlea culture without affecting the microtubule structure of the kinocilium. These results indicate critical role of Daple in hair bundle arrangement through the orchestration of apical microtubule distribution, and thereby in hearing, especially at high frequencies.