Impaired healing in an incision wound in corneal stroma in a lumican-null mouse.

Purpose: We investigated healing pattern of an incisional wound in corneal stroma of lumican-null (KO) mice.

Methods: C57BL/6 mice (wild-type, WT) and lumican-null (knockout, KO) mice were used. A linear full-thickness incision was produced in one cornea of each mouse.

Engineered Knockout of TRPA1 Inhibits Laser-Induced Choroidal Neovascularization Along With Associated TGFβ1 Expression and Neutrophil Infiltration.

We examined the effects of gene ablation and chemical inhibition of transient receptor potential ankyrin 1 (TRPA1) on the growth of experimental argon laser-induced choroidal neovascularization (CNV) in mice. CNV was induced in the eyes of 6- to 8-week-old TRPA1-null (knockout [KO]) and wild-type (WT) mice by argon laser irradiation. Gene expression analysis was performed in laser-injured tissues at days 1 and 3.

Loss of TRPV4 Cation Channel Inhibition of Macrophage Infiltration and Neovascularization in a Mouse Cornea.

Corneal injury-associated inflammation could induce inward-growing neovascularization from the periphery of the tissue. Such neovascularization could cause stromal opacification and curvature disturbance, and both potentially impair visual function. In this study, we determined the effects of the loss of transient receptor potential vanilloid 4 (TRPV4) expression on the development of neovascularization in the corneal stroma in mice by producing a cauterization injury in the central area of the cornea.

Impairment of corneal epithelial wound healing is association with increased neutrophil infiltration and reactive oxygen species activation in tenascin X-deficient mice.

The purpose of the study was to uncover the role of tenascin X in modulation of healing in mouse corneas subjected to epithelium debridement. Healing in corneas with an epithelial defect was evaluated at the levels of gene and protein expression. Wound healing-related mediators and inflammatory cell infiltration were detected by histology, immunohistochemistry and real-time RT-PCR.

Loss of sphingosine 1-phosphate receptor 3 gene function impairs injury-induced stromal angiogenesis in mouse cornea.

Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid generated through sphingosine kinase1 (SPK1)-mediated phosphorylation of sphingosine. We show here that injury-induced S1P upregulation increases corneal neovascularization through stimulating S1PR3, a cognate receptor. since this response was suppressed in S1PR3-knockout mice.

Inhibition of Rho kinase suppresses capsular contraction following lens injury in mice.

Purpose: We investigated the effect of systemic fasudil hydrochloride and an inhibitor of nuclear translocation of myocardin-related transcription factor-A (MRTF-A) on capsular contraction in a puncture-injured lens in mice.

Materials And Methods: Lens injury of an anterior capsular break was achieved in male adult C57Bl/6 mice under general and topical anesthesia at 1 h after systemic fasudil hydrochloride (intraperitoneal, 10 mg/kg body weight) or vehicle administration. The mice were allowed to heal after instillation of ofloxacin ointment, for 5 and 10 days with daily administration of fasudil hydrochloride or vehicle.

Cell-free DNA content in follicular fluid: A marker for the developmental ability of porcine oocytes.

Purpose: The present study examined the relationships among the amount of cell-free-DNA (cfDNA) in porcine follicular fluid (FF), the developmental ability of enclosed oocytes, and characteristics of granulosa cells and examined the effect of cfDNA content in maturation medium on the developmental ability of the oocytes.

Methods: Oocytes and FF were collected from individual gilts, and the gilts were rated based on the ability of their oocytes to develop to the blastocyst stage and the amount of cfDNA in the FF. The copy numbers of mitochondrial DNA (Mt-DNA) and nuclear DNA (N-DNA) were measured by real-time PCR and the DNA sequence.

Durable anticancer immunity from intratumoral administration of IL-23, IL-36γ, and OX40L mRNAs.

Many solid cancers contain dysfunctional immune microenvironments. Immune system modulators that initiate responses to foreign pathogens could be promising candidates for reigniting productive responses toward tumors. Interleukin-1 (IL-1) and IL-12 cytokine family members cooperate at barrier tissues after microbial invasion, in human inflammatory diseases, and in antitumoral immunity.

Suppression of neovascularization in corneal stroma in a TRPA1-null mouse.

Corneal neovascularization and inflammatory fibrosis induced by severe injury or infection leads to tissue opacification and even blindness. Transient receptor potential (TRP) channel subtypes contribute to mediating these maladaptive responses through their interactions with other receptors. TRPV1 is one of the contributing channel isoforms inducing neovascularization in an alkali burn mouse wound healing model.

Sensory nerve supports epithelial stem cell function in healing of corneal epithelium in mice: the role of trigeminal nerve transient receptor potential vanilloid 4.

In order to understand the pathobiology of neurotrophic keratopathy, we established a mouse model by coagulating the first branch of the trigeminal nerve (V1 nerve). In our model, the sensory nerve in the central cornea disappeared and remaining fibers were sparse in the peripheral limbal region. Impaired corneal epithelial healing in the mouse model was associated with suppression of both cell proliferation and expression of stem cell markers in peripheral/limbal epithelium as well as a reduction of transient receptor potential vanilloid 4 (TRPV4) expression in tissue.

Lack of plakoglobin impairs integrity and wound healing in corneal epithelium in mice.

We generated cornea-specific plakoglobin (Jup; junctional plakoglobin) knockout mice in order to investigate the function of plakoglobin on the maintenance of the homeostasis of corneal epithelium in mice. Cornea epithelium-specific conditional knockouts (Jup) (cKO) were obtained by breeding keratin12-Cre (Krt12-Cre) mice to Jup-floxed (Jup) mice. Light and transmission electron microscopic and immunohistochemical analyses were carried out to determine consequence of the loss of plakoglobin on maintaining corneal epithelium integrity under mechanical stress, e.

H3B-6527 Is a Potent and Selective Inhibitor of FGFR4 in FGF19-Driven Hepatocellular Carcinoma.

Activation of the fibroblast growth factor receptor FGFR4 by FGF19 drives hepatocellular carcinoma (HCC), a disease with few, if any, effective treatment options. While a number of pan-FGFR inhibitors are being clinically evaluated, their application to FGF19-driven HCC may be limited by dose-limiting toxicities mediated by FGFR1-3 receptors. To evade the potential limitations of pan-FGFR inhibitors, we generated H3B-6527, a highly selective covalent FGFR4 inhibitor, through structure-guided drug design.

Relationships between the amount of saliva and medications in elderly individuals.

Objective: To investigate medications that are related to volume of saliva in the elderly.

Background Data: In the elderly, many cases of mouth dryness may represent side effects of medication.

Materials And Methods: The volume of unstimulated saliva was measured for 30 s (cotton roll test), and with stimulation for 3 min (gum test) in 368 subjects 79-80 years old (177 men, 191 women).