ABSTRACT
Selaginella tamariscina is a perennial plant that is used for diverse diseases. This study investigated whether Selaginella tamariscina has an antiviral effect against influenza A virus (IAV) infection. We used green fluorescent protein (GFP)-tagged influenza A virus (IAV) to examine the effect of Selaginella tamariscina ethanol extract (STE) on influenza viral infection. Fluorescence microscopy and flow cytometry showed that STE potently represses GFP expression by the virus, dose-dependently. STE significantly inhibited the expression of the IAV M2, NP, HA, NA, NS1, and PB2 proteins. Time-of-addition and hemagglutination inhibition assays showed that STE has an inhibitory effect on hemagglutinin and viral binding on the cells at an early infection time. In addition, STE exerted a suppressive effect on the neuraminidase activity of the H1N1 and H3N2 IAVs. Furthermore, dose-dependently, STE inhibited the cytopathic effect induced by H3N2, as well as by H1N1 IAV. Especially in the presence of 200 µg/mL STE, the cytopathic effect was completely blocked. Our findings suggest that STE has antiviral efficacy against IAV infection; thus, it could be developed as a natural IAV inhibitor.
Subject(s)
Antiviral Agents , Ethanol , Influenza A Virus, H1N1 Subtype , Influenza A Virus, H3N2 Subtype , Neuraminidase , Plant Extracts , Selaginellaceae , Neuraminidase/antagonists & inhibitors , Neuraminidase/metabolism , Plant Extracts/pharmacology , Antiviral Agents/pharmacology , Influenza A Virus, H1N1 Subtype/drug effects , Humans , Influenza A Virus, H3N2 Subtype/drug effects , Animals , Madin Darby Canine Kidney Cells , Selaginellaceae/chemistry , Dogs , Influenza A virus/drug effects , Hemagglutinins/metabolism , Influenza, Human/drug therapyABSTRACT
Graft-versus-host disease is among the most common clinical complications following allogeneic hematopoietic stem cell transplantation. It causes inflammation-mediated destruction and dysfunction of various organ systems including ocular tissues in 60-90% of the patients and is termed ocular GVHD (oGVHD). In oGVHD, donor-derived T-cells recognize host antigens as foreign, resulting in immune dysregulation, inflammation and fibrosis of lacrimal glands, meibomian glands, cornea, and conjunctiva. The clinical presentation in oGVHD patients range from mild dry eye symptoms to catastrophic inflammation mediated pathological changes which can cause corneal perforation and blindness. In this review article, we provide detailed insights into the impact of mucosal barrier disruption, the afferent and efferent phases of immunological response involving activation of antigen presenting cells and T cells, respectively. We evaluate the evidence outlining the effector phase of the disease leading to cellular destruction and eventually fibrosis in patients with oGVHD. Finally, we discuss the well-established criteria for the diagnosis of oGVHD.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/etiology , Graft vs Host Disease/immunology , Eye Diseases/etiology , Eye Diseases/immunologyABSTRACT
Mesenchymal stromal cells (MSCs) have been shown to modulate the function of various subsets of T cells such as naïve CD4+ T cells and IFNγ+CD4+ Th1 cells; however, mechanisms underlying this regulation have not been fully deciphered. Our in vitro culture assays demonstrate that MSCs suppress the activation and function of CD4+ T cells by secreting interleukin 11, and neutralization of IL11 abrogates MSC-mediated suppression of CD4+ T cell function. Moreover, delayed-type, exogenous supplementation of IL11 significantly suppressed IFNγ+ expression by Th1 cells. Th1 and CD8+ cells play central roles in T cell-mediated tissue damage. Using a murine model of hypersensitivity response to study T cell-mediated tissue damage, we show that silencing IL11 in MSCs significantly abates the capacity of MSCs to suppress the generation of IFNγ-secreting CD4+ and CD8+ cells, failing to prevent T cell-mediated tissue inflammation and tissue damage.
Subject(s)
Interleukin-11 , Mesenchymal Stem Cells , Th1 Cells , Animals , Female , Mice , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cells, Cultured , Interferon-gamma/immunology , Interleukin-11/immunology , Mesenchymal Stem Cells/immunology , Mice, Inbred C57BL , Th1 Cells/immunologyABSTRACT
BACKGROUND: Angiosarcoma is an extremely rare malignant tumor. So far, only about 42 cases of angiosarcoma involving the eyelids have been reported. Eyelid angiosarcoma occurs more frequently in elderly Caucasian males and is prone to misdiagnosis. We present a case report in a young Asian male patient with eyelid angiosarcoma that was misdiagnosed as a chalazion. CASE PRESENTATION: A 46-year-old South Korean male with no underlying disease had a right lower lid mass. The lesion was initially misdiagnosed as a chalazion at a local clinic, but a diagnosis of eyelid angiosarcoma was made after the first biopsy trial. PET-CT was performed to ensure that there was no metastasis in the whole body. Surgical excision with enough surgical margin was used alone for treatment and reconstruction was performed with a tarsoconjunctival advancement flap (modified Hughes procedure), which helped ensure good cosmesis. No recurrence was observed 4 years and 5 months after the surgery. CONCLUSIONS: The current study presents the first case of chalazion-mimicked eyelid angiosarcoma in a young Asian male aged under 50 years. This case shows that even if a benign eyelid disease is suspected in a young patient, an incisional biopsy must be performed to confirm whether the lesion is malignant. Since the prognosis is good for the case of eyelid angiosarcoma, if there is no clear evidence of distal metastasis, surgical resection should be performed with an enough safety margin.
Subject(s)
Chalazion , Eyelid Neoplasms , Hemangiosarcoma , Aged , Male , Humans , Middle Aged , Chalazion/diagnosis , Eyelid Neoplasms/diagnosis , Eyelid Neoplasms/surgery , Eyelid Neoplasms/pathology , Hemangiosarcoma/diagnosis , Hemangiosarcoma/surgery , Hemangiosarcoma/pathology , Positron Emission Tomography Computed Tomography , Eyelids/surgery , Eyelids/pathologyABSTRACT
Advancements in neural interface technologies have enabled the direct connection of neurons and electronics, facilitating chemical communication between neural systems and external devices. One promising approach is a synaptogenesis-involving method, which offers an opportunity for synaptic signaling between these systems. Janus synapses, one type of synaptic interface utilizing synaptic cell adhesion molecules for interface construction, possess unique features that enable the determination of location, direction of signal flow, and types of neurotransmitters involved, promoting directional and multifaceted communication. This study presents the first successful establishment of a Janus synapse between dopaminergic (DA) neurons and abiotic substrates by using a neuroligin-2 (NLG2)-mediated synapse-inducing method. NLG2 immobilized on gold-coated microspheres can induce synaptogenesis upon contact with spatially isolated DA axons. The induced DA Janus synapses exhibit stable synaptic activities comparable to that of native synapses over time, suggesting their suitability for application in neural interfaces. By calling for DA presynaptic organizations, the NLG2-immobilized abiotic substrate is a promising tool for the on-site detection of synaptic dopamine release.
Subject(s)
Neuroligins , Presynaptic Terminals , Presynaptic Terminals/metabolism , Dopamine/metabolism , Microspheres , Neurons , Synapses/physiologyABSTRACT
Panax ginseng Meyer and Inula japonica Thunb. are well established in traditional medicine and are known for their therapeutic properties in managing a range of ailments such as diabetes, asthma, and cancer. Although P. ginseng and I. japonica can alleviate pulmonary fibrosis (PF), the anti-fibrosis effect on PF by the combination of two herbal medicines remains unexplored. Therefore, this study explores this combined effect. In conditions that were not cytotoxic, MRC-5 cells underwent treatment using the formula combining P. ginseng and I. japonica (ISE081), followed by stimulation with transforming growth factor (TGF)-ß1, to explore the fibroblast-to-myofibroblast transition (FMT). After harvesting the cells, mRNA levels and protein expressions associated with inflammation and FMT-related markers were determined to evaluate the antiinflammation activities and antifibrosis effect of ISE081. Additionally, the anti-migratory effects of ISE081 were validated through a wound-healing assay. ISE081 remarkably reduced the mRNA levels of interleukin (IL)-6, IL-8, α-smooth muscle actin (SMA), and TGF-ß1 in MRC-5 cells and suppressed the α-SMA and fibronectin expressions, respectively. Furthermore, ISE081 inhibited Smad2/3 phosphorylation and wound migration of MRC-5 cells. Under the same conditions, comparing those of ISE081, P. ginseng did not affect the expression of α-SMA, fibronectin, and Smad2/3 phosphorylation, whereas I. japonica significantly inhibited them but with cytotoxicity. The results indicate that the synergistic application of P. ginseng and I. japonica enhances the anti-fibrotic properties in pulmonary fibroblasts and concurrently diminishes toxicity. Therefore, ISE081 has the potential as a prevention and treatment herbal medicine for PF.
Subject(s)
Inula , Panax , Pulmonary Fibrosis , Humans , Inula/metabolism , Fibronectins/genetics , Fibronectins/metabolism , Panax/metabolism , Fibrosis , Pulmonary Fibrosis/metabolism , Fibroblasts , Transforming Growth Factor beta1/metabolism , RNA, Messenger/metabolismABSTRACT
Incidental pulmonary nodules detected via computed tomography (CT) are usually small, solid nodules (diameters less than 8 mm) that are likely benign and are difficult to biopsy. Additional features of the benignity of these small nodules may help determine the need and periodicity of further follow-up and should be identified. This study was conducted to examine the clinical factors associated with benign solid pulmonary nodules measuring less than 8 mm in diameter. This retrospective study enrolled participants who underwent low-dose chest CT scans for 3 consecutive years during routine health check-ups at a university hospital in Korea. We chose a 2-year study period to ensure that the nodule(s) were benign, which meant there was no interval change over this period. Participants were stratified into two groups: no nodule (n = 56) and nodule(s) (n = 355). Multivariable logistic regression analyses were performed to explore associations (adjusted odds ratio [aOR], 95% confidence interval [CI], p-value) between variables and nodule(s). In this study cohort, elevated levels of low-density lipoprotein (LDL) cholesterol were positively associated factors with the presence of benign pulmonary nodule(s) (aOR: 1.10, 95% CI:1.00-1.20, p = 0.0488), whereas current cigarette smoking was negatively associated with nodules (aOR: 0.26, 95% CI: 0.08-0.81, p = 0.0202). Therefore, an elevated LDL cholesterol level was the only factor that was positively associated with the presence of benign small pulmonary nodules.
ABSTRACT
Purpose: Regulation of inflammation is critical for achieving favorable outcomes in wound healing. In this study, we determine the functional role and mechanism of action of IL-11, an immunomodulatory cytokine, in regulating inflammatory response at the ocular surface. Methods: Corneal injury was induced by mechanical removal of the epithelium and anterior stroma using an AlgerBrush II. Transcript and protein levels of IL-11 in injured cornea were quantified using real-time PCR and ELISA analysis. Corneal inflammation was assessed by measuring frequencies of total CD45+ inflammatory cells, CD11b+Ly6G+ polymorphonuclear cells (neutrophils), and CD11b+Ly6G- mononuclear cells (macrophages, monocytes) at the ocular surface using flow cytometry. To assess the effect of IL-11 on innate immune cell function, cell activation marker and inflammatory cytokines including major histocompatibility complex (MHC) class II, myeloperoxidase (MPO), TNFα, and inducible nitric oxide synthase (iNOS) were measured following recombinant IL-11 treatment (1 µg/mL). Injured corneas were topically treated with IL-11 (1 µg/mL), and wound healing was evaluated using corneal fluorescein staining. Results: Corneal injury resulted in increased levels of IL-11 in the cornea, particularly in the stroma. Neutrophils and CD11b+ mononuclear cells (macrophages, monocytes) substantially expressed IL-11 receptor. Interestingly, IL-11 significantly downregulated the activation of immune cells, as evidenced by the lower expression of MHC II and TNFα by CD11b+ mononuclear cells and lower levels of MPO by neutrophils. Topical administration of IL-11 to injured corneas led to faster wound healing and better retention of tissue architecture. Conclusions: Our findings demonstrate IL-11 is a key modulator of ocular surface inflammation and provide novel evidence of IL-11 as a potential therapeutic to control inflammatory damage and accelerate wound repair following injury.
Subject(s)
Corneal Injuries , Interleukin-11 , Cornea , Corneal Injuries/drug therapy , Cytokines , Inflammation , Tumor Necrosis Factor-alpha , Animals , MiceABSTRACT
Thuja orientalis Folium (TOF) has been prescribed traditionally as an expectorant for inflammatory airway disease. In this study, we evaluated the anti-influenza A virus (IAV) activity of TOF by detecting GFP expressed by influenza A virus (A/PR/8/34-GFP) infection. The fluorescence microscopy and fluorescence-activated cell sorting analysis showed that TOF potently inhibited IAV infection, dose-dependently. Consistently, immunofluorescence and Q-PCR analysis results confirmed TOF significantly represses IAV protein and RNA expression. TOF inhibited IAV infection at the binding and entry step upon viral infection and interferes with HA protein. Further, TOF exhibited a virucidal effect and inhibited the neuraminidase activity of IAV. Additionally, TOF prevented the cytopathic effect caused by H1N1 and H3N2 IAV infection. Amentoflavone among the constituents in TOF exerted the strongest anti-IAV effect. Myricetin, quercetin, and quercitrin also inhibited IAV infection. However, the potent anti-IAV effect of TOF may be related to the synergistic effect of constituents, not by a single specific compound. Our results suggest TOF exhibits a significant inhibitory effect against IAV infection at multi-stages via the blockage of viral attachment and entry, inhibition of neuraminidase, and induction of virucidal effects.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza A virus , Influenza, Human , Thuja , Humans , Antiviral Agents/pharmacology , Antiviral Agents/metabolism , Thuja/metabolism , Influenza A Virus, H1N1 Subtype/genetics , Influenza A Virus, H3N2 Subtype/genetics , Neuraminidase/geneticsABSTRACT
Purpose: To evaluate the cases of retinal vessel occlusion following COVID-19 vaccination and evaluate the onset interval and clinical presentations in patients diagnosed with vaccine associated retinal artery occlusion (RAO) and retinal vein occlusion (RVO). Design: Retrospective study of the cases reported to the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS) between December 11, 2020 and July 1, 2022. Participants: Patients diagnosed with retinal vessel occlusion following vaccination with BNT162b2, mRNA-1273, and Ad26.COV2.S globally. Methods: We performed a descriptive analysis of the patient demographics and clinical presentation in patients with retinal vessel occlusion. The correlation between the vaccines and continuous and categorical variables were assessed. We performed the post-hoc analysis to evaluated the association between RAO and RVO onset post-vaccination, and vaccine and dosage. Finally, a 30-day reverse analysis for RAO and RVO onset following administration of vaccine. A major limitation in the methods of this study is the lack of control group for assessing the risk of retinal vessel occlusive disease in patients who received the vaccine compared to the patients who were unvaccinated. Main Outcome Measures: The crude reporting rate of retinal vessel occlusion following SARS-CoV-2 vaccine. The ocular and systemic presentations, onset duration and short term risk of RAO and RVO following vaccination. Results: During the study period, 1351 retinal vessel occlusion cases were reported globally. The crude reporting rates of retinal vessel occlusion for BNT162b2, mRNA-1273, and Ad26.COV2.S were 0.36, 0.41, and 0.69, respectively. The majority of the retinal vessel occlusion cases were reported following BNT162b2 (n=606, 74.17%). The mean age of patients with RVO and RAO was 58.54 ± 16.06 years and 64.63 ± 16.16 years, respectively. In the cohort, 817 and 433 patients were diagnosed with RVO and RAO, respectively. Most cases of RVO (41.12%) and RAO (48.27%) were reported within the first week post-vaccination. We observed that the mean onset interval for RVO was significantly longer in patients who received Ad26.Cov2.S (54.07 ± 88.98 days) compared to BNT162b2 (18.07 ± 28.66 days) and mRNA-1273 (22.85 ± 38.13 days) vaccines (p<0.0001). This was further confirmed by post-hoc analysis, which revealed a significantly longer onset duration for the Ad26.Cov2.S compared to BNT162b2 and mRNA 1273 vaccines (p<0.0001). The reverse Kaplan Meier 30-day risk analysis showed a significant a higher risk of RVO onset following BNT162b2 compared to other vaccines(p<0.0001). Conclusions: The low crude reporting rate highlights a low safety concern for retinal vessel occlusion following SARS-CoV-2 vaccination. This study provides insights into possible temporal association between reported retinal vessel occlusion events with SARS-CoV-2 vaccines, however further insights are needed to understand the underlying immunopathological mechanisms that promote thrombosis of retinal vasculature on vaccine administration.
ABSTRACT
Lilii Bulbus, the bulb of tiger lily, has anti-oxidant and anti-tumorigenic properties. However, the effects of Lilii Bulbus on learning, memory, and hippocampal neurogenesis remain unknown. This study investigated whether water extract of Lilii Bulbus (WELB) affects memory ability and hippocampal neurogenesis. Behavioral analyses (Morris water maze and passive avoidance test), immunohistochemistry, cell proliferation assay, and immunoblot analysis were performed. WELB (50 and 100 mg/kg; for 14 days) enhanced memory retention and spatial memory in normal mice as well as in scopolamine-treated mice with memory deficits. Furthermore, the administration of WELB significantly increased the number of proliferating cells and surviving newborn cells in the dentate gyrus of the hippocampus in normal mice. We found that WELB has a pro-neurogenic effect by increasing the activation of brain-derived neurotrophic factor (BDNF)/cAMP response element-binding protein (CREB) and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) in the hippocampus. Moreover, we confirmed that WELB (100 and 200 µg/ml) significantly increased NE-4 C and primary embryonic NSCs proliferation. Inhibition/knockdown of MEK/ERK blocked WELB-induced MEK/ERK phosphorylation and NSCs proliferation. Hence, MEK/ERK activation was required in WELB-induced NSCs proliferation. Our study demonstrates the first evidence for WELB promoting hippocampal neurogenesis and memory; pro-neurogenic activity may enhance brain plasticity, with implications for treating neurodegenerative diseases.
Subject(s)
Extracellular Signal-Regulated MAP Kinases , Hippocampus , Mice , Animals , Extracellular Signal-Regulated MAP Kinases/metabolism , Neurogenesis , Spatial Memory , Mitogen-Activated Protein Kinase Kinases/metabolism , Maze LearningABSTRACT
Seamless neural interfaces conjoining neurons and electrochemical devices hold great potential for highly efficient signal transmission across neural systems and the external world. Signal transmission through chemical sensing and stimulation via electrochemistry is remarkable because communication occurs through the same chemical language of neurons. Emerging strategies based on synaptic interfaces, iontronics-based neuromodulation, and improvements in selective neurosensing techniques have been explored to achieve seamless integration and efficient neuro-electronics communication. Synaptic interfaces can directly exchange signals to and from neurons, in a similar manner to that of chemical synapses. Hydrogel-based iontronic chemical delivery devices are operationally compatible with neural systems for improved neuromodulation. In this perspective, we explore developments to improve the interface between neurons and electrodes by targeting neurons or sub-neuronal regions including synapses. Furthermore, recent progress in electrochemical neurosensing and iontronics-based chemical delivery is examined.
ABSTRACT
Isatidis folium or Isatis tinctoria L. is a flowering plant of the Brassicaceae family, commonly known as woad, with an ancient and well-documented history as an indigo dye and medicinal plant. This study aimed to evaluate the anti-atopic dermatitis (AD) effects of Isatidis folium water extract (WIF) using a 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mouse model and to investigate the underlying mechanism using tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-activated HaCaT cells. Oral administration of WIF reduced spleen weight, decreased serum IgE and TNF-α levels, reduced epidermal and dermal thickness, and inhibited eosinophil and mast cell recruitment to the dermis compared to DNCB-induced control groups. Furthermore, oral WIF administration suppressed extracellular signal-regulated kinase and p38 mitogen-activated protein kinase protein expression levels, p65 translocation from the cytoplasm to the nucleus, and mRNA expression of TNF-α, IFN-γ, interleukin (IL)-6, and IL-13 in skin lesion tissues. In HaCaT cells, WIF suppressed the production of regulated upon activation, normal T cell expressed and secreted (RANTES), thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), MCP-1, and MIP-3a, which are inflammatory cytokines and chemokines related to AD, and inhibited the mRNA expression of RANTES, TARC, and MDC in TNF-α/IFN-γ-stimulated HaCaT cells. Overall, the results revealed that WIF ameliorated AD-like skin inflammation by suppressing proinflammatory cytokine and chemokine production via nuclear factor-κB pathway inhibition, suggesting WIF as a potential candidate for AD treatment.
Subject(s)
Dermatitis, Atopic , Tumor Necrosis Factor-alpha , Animals , Mice , Humans , Tumor Necrosis Factor-alpha/metabolism , Dinitrochlorobenzene/adverse effects , Dinitrochlorobenzene/metabolism , Keratinocytes , Interferon-gamma/metabolism , Water/metabolism , HaCaT Cells , Dermatitis, Atopic/chemically induced , Dermatitis, Atopic/drug therapy , Dermatitis, Atopic/metabolism , Cytokines/metabolism , NF-kappa B/metabolism , Chemokines/metabolism , RNA, Messenger/geneticsABSTRACT
Mounting evidence suggests mesenchymal stromal cells (MSCs) suppress CD4+ T-cell activation, but whether MSCs directly regulate activation and expansion of allogeneic T cells has not been fully deciphered. Here, we identified that both human and murine MSCs constitutively express ALCAM, a cognate ligand for CD6 receptors on T cells, and investigated its immunomodulatory function using in vivo and in vitro experiments. Our controlled coculture assays demonstrated that ALCAM-CD6 pathway is critical for MSCs to exert its suppressive function on early CD4+CD25- T-cell activation. Moreover, neutralizing ALCAM or CD6 results in the abrogation of MSC-mediated suppression of T-cell expansion. Using a murine model of delayed-type hypersensitivity response to alloantigen, we show that ALCAM-silenced MSCs lose the capacity to suppress the generation of alloreactive IFNγ-secreting T cells. Consequently, MSCs, following ALCAM knockdown, failed to prevent allosensitization and alloreactive T-cell-mediated tissue damage.
Subject(s)
Activated-Leukocyte Cell Adhesion Molecule , Mesenchymal Stem Cells , Mice , Humans , Animals , Activated-Leukocyte Cell Adhesion Molecule/metabolism , CD4-Positive T-Lymphocytes/metabolism , Coculture Techniques , Lymphocyte Activation , Cells, CulturedSubject(s)
Antiviral Agents , COVID-19 , Kidney Failure, Chronic , Renal Insufficiency, Chronic , Humans , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/therapy , Hydroxylamines/therapeutic use , Kidney Failure, Chronic/complications , Renal Insufficiency, Chronic/complications , Ritonavir/therapeutic useABSTRACT
INTRODUCTION: This study was conducted to explore factors associated with smoking cessation in male smokers with cardiovascular disease (CVD) or cancer, the two leading causes of death worldwide, and to compare them with quitting factors in smokers without the two diseases. METHODS: This is a secondary dataset analysis of the Korea National Health and Nutrition Examination Survey (KNHANES), nationally representative data from 2008-2019 (excluding 2013-2014), and included 12998 men without CVD or cancer (group without CVD or cancer), 1027 men with CVD (CVD group), and 616 men with cancer (cancer group). A Wald test with multiple logistic regression analysis was conducted. RESULTS: The quitting success rates in the CVD and cancer groups were consistently higher than those in the group without CVD or cancer. Old age and willpower in the CVD group, and old age and being married in the cancer group were associated with quitting success. Secondhand smoking and methods of quitting other than willpower were related to quitting failure in both groups. When interaction effects between the groups were examined, household income was the only factor associated with successful cessation in the group without CVD or cancer (AOR=1.17, 1.18, and 1.40, among the second, third, and fourth highest income quartiles, respectively; p for interaction=0.023). Higher smoking amounts (AOR=0.85; p<0.001) and poor health perception (AOR=0.64; p=0.035) were associated with quitting failure in the group without CVD or cancer. However, no significant factor was detected related to smoking cessation in both the CVD and cancer groups when the interaction effect was investigated. CONCLUSIONS: The quitting success rates in the CVD and cancer groups were higher, but no disease-specific quitting factors were identified. Therefore, being diagnosed with CVD or cancer itself could be inferred as a motive for quitting smoking.
ABSTRACT
Prevention of inflammatory angiogenesis is critical for suppressing chronic inflammation and inhibiting inflammatory tissue damage. Angiogenesis is particularly detrimental to the cornea because pathologic growth of new blood vessels can lead to marked vision impairment and even loss of vision. The expression of proinflammatory cytokines by injured tissues exacerbates the inflammatory cascade, including angiogenesis. IL-36 cytokine, a subfamily of the IL-1 superfamily, consists of three proinflammatory agonists, IL-36α, IL-36ß, and IL-36γ, and an IL-36 receptor antagonist (IL-36Ra). Data from the current study indicate that human vascular endothelial cells constitutively expressed the cognate IL-36 receptor. The current investigation, for the first time, characterized the direct contribution of IL-36γ to various angiogenic processes. IL-36γ up-regulated the expression of vascular endothelial growth factors (VEGFs) and their receptors VEGFR2 and VEGFR3 by human vascular endothelial cells, suggesting that IL-36γ mediates the VEGF-VEGFR signaling by endothelial cells. Moreover, by using a naturally occurring antagonist IL-36Ra in a murine model of inflammatory angiogenesis, this study demonstrated that blockade of endogenous IL-36γ signaling results in significant retardation of inflammatory angiogenesis. The current investigation on the proangiogenic function of IL-36γ provides novel evidence of the development of IL-36γ-targeting strategies to hamper inflammatory angiogenesis.
Subject(s)
Corneal Diseases , Endothelial Cells , Interleukin-1 , Neovascularization, Pathologic , Vascular Endothelial Growth Factor A , Animals , Humans , Mice , Corneal Diseases/genetics , Corneal Diseases/immunology , Corneal Diseases/pathology , Cytokines , Endothelial Cells/metabolism , Interleukin-1/genetics , Interleukin-1/metabolism , Neovascularization, Pathologic/genetics , Neovascularization, Pathologic/immunology , Neovascularization, Pathologic/pathology , Receptors, Vascular Endothelial Growth Factor/genetics , Receptors, Vascular Endothelial Growth Factor/immunology , Vascular Endothelial Growth Factor Receptor-2ABSTRACT
The lacrimal gland undergoes significant structural and functional deterioration with aging. Marked with increased inflammation and fibrosis, the aged lacrimal gland is unable to perform its protective function. As a result, the ocular surface becomes highly susceptible to various ocular surface pathologies, including corneal epitheliopathy. We and others have previously shown that mast cells mediate tissue inflammation by recruiting other immune cells. However, despite their well-known characteristics of secreting various inflammatory mediators, whether mast cells contribute to the immune cell aggregation and activation, and acinar dystrophy of the aged lacrimal gland has not been investigated. Here, we demonstrate the role of mast cells in age-related lacrimal gland pathophysiology using mast cell-deficient (cKitw-sh) mice. Our data demonstrated a significant increase in mast cell frequencies and immune cell infiltration in the lacrimal gland of aged mice. Interestingly, mast cell deficiency resulted in a substantial reduction in inflammation and preservation of lacrimal gland structure, suggesting that mast cells mediate the aging process of the lacrimal gland.
ABSTRACT
BACKGROUND: A choristoma is defined as a growth of histologically normal tissue in an abnormal location. Epibulbar osseous choristoma is the rarest type among all ocular choristoma with less than 100 cases reported. Here, we report a case of epibulbar osseous choristoma combined with dermolipoma and a literature review. METHODS: A 15-year-old female patient presented with an accidentally found subconjunctival mass in her left eye. Slit lamp examination revealed a 10â ×â 10 mm elevated, sigmoid-shaped mass in the supratemporal quadrant of the bulbar conjunctiva. We performed a debulking excisional biopsy of the mass. RESULTS: The pathology confirmed osseous tissue surrounded by mature adipose tissue. At 1 week after the operation, the wound was clear and the patient was satisfied with the treatment. A systematic literature review of 14 previously published cases taken from PubMed dating back to 1987 along with ours was undertaken. The average age at presentation was 11.6 years and there was a female preponderance with 10 cases being female and the other 5 cases being male. Supratemporal conjunctiva was the most common site of presentation. There was no systemic disease associated with any of the cases. Since it is a benign tumor, it can be managed by observation, but if necessary, it can be treated by surgical removal. CONCLUSION: In pediatric subconjunctival mass, particularly located in supratemporal quadrant of bulbar conjunctiva, osseous choristoma should be considered in the differential diagnosis. Pre-operative CT scans will helpful to not also reduce complication with surgical excision but also helpful in prediction of diagnosis and prognosis.