Therapeutic Effects of Tacrolimus Ointment for Refractory Ocular Surface Inflammatory Diseases

Background: Amniotic Fluid Derived Mesenchymal Stem Cells (AF-MSCs) are adult, fibroblast- like, self-renewable, multipotent stem cells. During the last decade, the therapeutic potential of AF-MSCs, based on their huge differentiation capacity and immunomodulatory characteristics, has been extensively explored in animal models of degenerative and inflammatory diseases. Objective: In order to describe molecular mechanisms responsible for the therapeutic effects of AFMSCs, we summarized current knowledge about phenotype, differentiation potential and immunosuppressive properties of AF-MSCs. Methods: An extensive literature review was carried out in March 2018 across several databases (MEDLINE, EMBASE, Google Scholar), from 1990 to present. Keywords used in the selection were: “amniotic fluid derived mesenchymal stem cells”, “cell-therapy”, “degenerative diseases”, “inflammatory diseases”, “regeneration”, “immunosuppression”. Studies that emphasized molecular and cellular mechanisms responsible for AF-MSC-based therapy were analyzed in this review. Results: AF-MSCs have huge differentiation and immunosuppressive potential. AF-MSCs are capable of generating cells of mesodermal origin (chondrocytes, osteocytes and adipocytes), neural cells, hepatocytes, alveolar epithelial cells, insulin-producing cells, cardiomyocytes and germ cells. AF-MSCs, in juxtacrine or paracrine manner, regulate proliferation, activation and effector function of immune cells. Due to their huge differentiation capacity and immunosuppressive characteristic, transplantation of AFMSCs showed beneficent effects in animal models of degenerative and inflammatory diseases of nervous, respiratory, urogenital, cardiovascular and gastrointestinal system. Conclusion: Considering the fact that amniotic fluid is obtained through routine prenatal diagnosis, with minimal invasive procedure and without ethical concerns, AF-MSCs represents a valuable source for cell-based therapy of organ-specific or systemic degenerative and inflammatory diseases.

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Development of Cytomegalovirus Corneal Endotheliitis During Long-Term Topical Tacrolimus and Steroid Treatment for Chronic Ocular Surface Inflammatory Diseases

Cornea ◽

10.1097/ico.0000000000002674 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Hideaki Yokogawa ◽

Akira Kobayashi ◽

Yuko Takemoto ◽

Natsuko Mori ◽

Ryotaro Wajima ◽

...

Keyword(s):

Ocular Surface ◽

Inflammatory Diseases ◽

Steroid Treatment ◽

Topical Tacrolimus ◽

Corneal Endotheliitis

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Increased Expression of Granzyme B and Transforming Growth Factor-β in Intralesional Plasma of Oral Lichenoid Reactions: A Preliminary Study

10.21203/rs.3.rs-112771/v1 ◽

2020 ◽

Author(s):

Kai Sun ◽

Lei Pan ◽

Yi-wen Deng ◽

Jun Chen ◽

Guan-huan Du ◽

...

Keyword(s):

Transforming Growth Factor ◽

Inflammatory Diseases ◽

Granzyme B ◽

Large Population ◽

Therapeutic Effects ◽

Peripheral Plasma ◽

Cytokine Profiles ◽

Tnf Α ◽

Lichenoid Reactions ◽

Tgf Β1

Abstract Background: Oral lichenoid reactions are intractable inflammatory diseases of oral mucosa. The cytokine profiles of intralesional blood remain unclear. We aim at revealing the intralesional cytokine profiles and providing some actual and stable intralesional cytokine biomarkers to evaluate the severity and therapeutic effects of oral lichenoid reactions.Methods: Paired intralesional and peripheral plasma from 26 patients with oral lichenoid reactions were collected. The concentration of 15 cytokines of granzyme B, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL17A, TNF-α, IFN-α, IFN-β, IFN-γ, TGF-β1, TGF-β2 and TGF-β3 was measured by Luminex assays. REU score was used for evaluating the severity of the disease. Results: Eleven cytokines including IL-10, IFN-α, IL-6, IL-17A, granzyme B, TGF-β1, TGF-β2, TGF-β3, IL-2, TNF-α, IL-12p70 were detected within the reliable working range. IL-10 was detected in less intralesional samples (19/26) than peripheral samples (26/26, p=0.01). The cytokine concentrations from intralesional plasma were significantly elevated in granzyme B (median 108.94 vs. 16.00), TGF-β1 (mean 30448.92 vs. 10199.04), TGF-β2 (mean 1659.73 vs. 1308.49) and TGF-β3 (mean 914.33 vs. 573.13) than that in peripheral plasma (p=0.001, p＜0.001, p＜0.001 and p＜0.001, respectively). The concentration of IL-12p70 in peripheral plasma was positively correlated with REU score (coefficient of correlation=0.463, p=0.02).Conclusions: The concentration of granzyme B and TGF-β are more abundant in intralesional microenvironment than in peripheral plasma of oral lichenoid reactions. IL-12p70 may be a potential molecular biomarker for evaluating the severity of oral lichenoid reactions. Cohort study of large population is required.

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Hwangryunhaedok-Tang Exerts Neuropreventive Effect on Memory Impairment by Reducing Cholinergic System Dysfunction and Inflammatory Response in a Vascular Dementia Rat Model

Molecules ◽

10.3390/molecules24020343 ◽

2019 ◽

Vol 24 (2) ◽

pp. 343 ◽

Cited By ~ 7

Author(s):

Eunjin Sohn ◽

Yu Kim ◽

Hye-Sun Lim ◽

Bu-Yeo Kim ◽

Soo-Jin Jeong

Keyword(s):

Vascular Dementia ◽

Rat Model ◽

Memory Impairment ◽

Neuronal Damage ◽

Inflammatory Diseases ◽

Ethanol Extract ◽

Mitogen Activated Protein Kinase ◽

Therapeutic Effects ◽

Sprague Dawley ◽

Cholinergic Dysfunction

Hwangryunhaedok-tang (HRT) is a traditional oriental herbal formula used in Asian countries for treating inflammatory diseases and controlling fever. Our present study aimed to determine whether HRT has therapeutic effects for patients with vascular dementia (VaD) using a bilateral common carotid artery occlusion (BCCAO) rat model and assessing spatial memory impairment and activation of neuroinflammation. BCCAO was performed in male Sprague Dawley rats to induce VaD, and oral HRT was administered daily for 30 d. Our data showed that HRT ameliorated BCCAO-induced memory and cognitive impairment in behavioral tests. In addition, HRT reversed cholinergic dysfunction and neuronal damage in the hippocampus of BCCAO rats. Furthermore, HRT attenuated microglial activation and reduced the phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase (JNK) induced by BCCAO. Simultaneous high-performance liquid chromatography analysis of HRT using index compounds from the herbal composition revealed that both HRT ethanol extract and commercial HRT granules primarily comprise geniposide, baicalin, and berberine. Our study showed that HRT administration resulted in the prevention of neuronal injury induced by BCCAO through improvement of cholinergic dysfunction and inhibition of neuroinflammatory responses, suggesting that HRT may have potential as a treatment for VaD.

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A Synthetic Cell-Penetrating Heparin-Binding Peptide Derived from BMP4 with Anti-Inflammatory and Chondrogenic Functions for the Treatment of Arthritis

International Journal of Molecular Sciences ◽

10.3390/ijms21124251 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4251

Author(s):

Da Hyeon Choi ◽

Dongwoo Lee ◽

Beom Soo Jo ◽

Kwang-Sook Park ◽

Kyeong Eun Lee ◽

...

Keyword(s):

Inflammatory Diseases ◽

Combined Treatment ◽

Therapeutic Effects ◽

Heparin Binding ◽

Rheumatic Arthritis ◽

Binding Peptide ◽

Human Knee ◽

Synthetic Cell ◽

Cell Penetrating ◽

Anti Inflammatory

We report dual therapeutic effects of a synthetic heparin-binding peptide (HBP) corresponding to residues 15–24 of the heparin binding site in BMP4 in a collagen-induced rheumatic arthritis model (CIA) for the first time. The cell penetrating capacity of HBP led to improved cartilage recovery and anti-inflammatory effects via down-regulation of the iNOS-IFNγ-IL6 signaling pathway in inflamed RAW264.7 cells. Both arthritis and paw swelling scores were significantly improved following HBP injection into CIA model mice. Anti-rheumatic effects were accelerated upon combined treatment with Enbrel® and HBP. Serum IFNγ and IL6 concentrations were markedly reduced following intraperitoneal HBP injection in CIA mice. The anti-rheumatic effects of HBP in mice were similar to those of Enbrel®. Furthermore, the combination of Enbrel® and HBP induced similar anti-rheumatic and anti-inflammatory effects as Enbrel®. We further investigated the effect of HBP on damaged chondrocytes in CIA mice. Regenerative capacity of HBP was confirmed based on increased expression of chondrocyte biomarker genes, including aggrecan, collagen type II and TNFα, in adult human knee chondrocytes. These findings collectively support the utility of our cell-permeable bifunctional HBP with anti-inflammatory and chondrogenic properties as a potential source of therapeutic agents for degenerative inflammatory diseases.

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Topical Ectoine: A Promising Molecule in the Upper Airways Inflammation—A Systematic Review

BioMed Research International ◽

10.1155/2019/7150942 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Manuele Casale ◽

Antonio Moffa ◽

Samanta Carbone ◽

Francesca Fraccaroli ◽

Andrea Costantino ◽

...

Keyword(s):

Inflammatory Diseases ◽

Selection Process ◽

Topical Administration ◽

Therapeutic Effects ◽

Upper Respiratory Tract ◽

Upper Airways ◽

Chronic Inflammatory Diseases ◽

High Concentrations ◽

Tract Infections ◽

Pharmacologic Agents

To date, topical therapies guarantee a better delivery of high concentrations of pharmacologic agents to the mucosa of the upper airways (UA). Recently, topical administration of ectoine has just been recognized as adjuvant treatment in the Allergic Rhinitis (AR) and Rhinosinusitis (ARS). The aim of this work is to review the published literature regarding all the potential therapeutic effects of ectoine in the acute and chronic inflammatory diseases of UA. Pertinent studies published without temporal limitation were selected searching on MEDLINE the following terms: “ectoine” and “nasal spray,” “oral spray,” “upper respiratory tract infections,” “rhinosinusitis,” “rhinitis,” “rhinoconjunctivitis,” “pharyngitis,” and “laryngitis.” At the end of our selection process, six relevant publications were included: two studies about the effect of ectoine on AR, one study about ARS, one study about rhinitis sicca anterior, and two studies about acute pharyngitis and/or laryngitis. Due to its moisturizing and anti-inflammatory properties, topical administration of ectoine could play a potential additional role in treatment of acute and chronic inflammatory diseases of UA, in particular in the management of sinonasal conditions improving symptoms and endoscopic findings. However, these results should be viewed cautiously as they are based on a limited number of studies; some of them were probably underpowered because of their small patient samples.

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A Mixed Micellar Formulation for the Transdermal Delivery of an Indirubin Analog

Pharmaceutics ◽

10.3390/pharmaceutics12020175 ◽

2020 ◽

Vol 12 (2) ◽

pp. 175

Author(s):

Seol Hwa Seo ◽

Eunhwan Kim ◽

Yechan Joo ◽

Juseung Lee ◽

Kyung Taek Oh ◽

...

Keyword(s):

Transdermal Delivery ◽

Myeloid Leukemia ◽

Active Component ◽

Water Solubility ◽

Inflammatory Diseases ◽

Human Cancer ◽

Tween 80 ◽

Skin Penetration ◽

Therapeutic Effects ◽

Peg 400

Indirubin is an active component of Dang Gui Long Hui Wan, which has been used in traditional Chinese medicine to treat inflammatory diseases as well as for the prevention and treatment of human cancer, such as chronic myeloid leukemia. The therapeutic effects of indirubin analogs have been underestimated due to its poor water solubility and low bioavailability. To improve the solubility and bioavailability of indirubin analogs, we prepared a mixed micellar formulation with Kolliphor® EL and Tween 80 as surfactants, and PEG 400 as a co-surfactant, followed by complexation with (2-hydroxyproply)-β-cyclodextrin at appropriate ratios. Overall, improving the solubility and skin penetration of indirubin analogs can increase clinical efficacy and provide maximum flux through the skin.

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Deficient CD40-TRAF6 signaling in leukocytes prevents atherosclerosis by skewing the immune response toward an antiinflammatory profile

Journal of Experimental Medicine ◽

10.1084/jem.20091293 ◽

2010 ◽

Vol 207 (2) ◽

pp. 391-404 ◽

Cited By ~ 163

Author(s):

Esther Lutgens ◽

Dirk Lievens ◽

Linda Beckers ◽

Erwin Wijnands ◽

Oliver Soehnlein ◽

...

Keyword(s):

Immune Responses ◽

Inflammatory Diseases ◽

Tumor Necrosis Factor Receptor ◽

Cd40 Ligand ◽

Therapeutic Effects ◽

Signaling Axis ◽

Plaque Phenotype ◽

Necrosis Factor

The CD40–CD40 ligand (CD40L) signaling axis plays an important role in immunological pathways. Consequently, this dyad is involved in chronic inflammatory diseases, including atherosclerosis. Inhibition of CD40L in apolipoprotein E (Apoe)–deficient (Apoe−/−) mice not only reduced atherosclerosis but also conferred a clinically favorable plaque phenotype that was low in inflammation and high in fibrosis. Blockade of CD40L may not be therapeutically feasible, as long-term inhibition will compromise systemic immune responses. Conceivably, more targeted intervention strategies in CD40 signaling will have less deleterious side effects. We report that deficiency in hematopoietic CD40 reduces atherosclerosis and induces features of plaque stability. To elucidate the role of CD40–tumor necrosis factor receptor-associated factor (TRAF) signaling in atherosclerosis, we examined disease progression in mice deficient in CD40 and its associated signaling intermediates. Absence of CD40-TRAF6 but not CD40-TRAF2/3/5 signaling abolishes atherosclerosis and confers plaque fibrosis in Apoe−/− mice. Mice with defective CD40-TRAF6 signaling display a reduced blood count of Ly6Chigh monocytes, an impaired recruitment of Ly6C+ monocytes to the arterial wall, and polarization of macrophages toward an antiinflammatory regulatory M2 signature. These data unveil a role for CD40–TRAF6, but not CD40–TRAF2/3/5, interactions in atherosclerosis and establish that targeting specific components of the CD40–CD40L pathway harbors the potential to achieve therapeutic effects in atherosclerosis.

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From Blood to the Brain: Can Systemically Transplanted Mesenchymal Stem Cells Cross the Blood-Brain Barrier?

Stem Cells International ◽

10.1155/2013/435093 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 34

Author(s):

Linan Liu ◽

Mark A. Eckert ◽

Hamidreza Riazifar ◽

Dong-Ku Kang ◽

Dritan Agalliu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Brain Tumors ◽

Blood Brain Barrier ◽

Inflammatory Diseases ◽

Neurological Diseases ◽

Brain Barrier ◽

Therapeutic Effects ◽

Blood Brain ◽

The Brain

Systemically infused mesenchymal stem cells (MSCs) are emerging therapeutics for treating stroke, acute injuries, and inflammatory diseases of the central nervous system (CNS), as well as brain tumors due to their regenerative capacity and ability to secrete trophic, immune modulatory, or other engineered therapeutic factors. It is hypothesized that transplanted MSCs home to and engraft at ischemic and injured sites in the brain in order to exert their therapeutic effects. However, whether MSCs possess the ability to migrate across the blood-brain barrier (BBB) that separates the blood from the brain remains unresolved. This review analyzes recent advances in this area in an attempt to elucidate whether systemically infused MSCs are able to actively transmigrate across the CNS endothelium, particularly under conditions of injury or stroke. Understanding the fate of transplanted MSCs and their CNS trafficking mechanisms will facilitate the development of more effective stem-cell-based therapeutics and drug delivery systems to treat neurological diseases and brain tumors.

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4-Methoxycarbonyl Curcumin: A Unique Inhibitor of Both Inflammatory Mediators and Periodontal Inflammation

Mediators of Inflammation ◽

10.1155/2013/329740 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 11

Author(s):

Ying Gu ◽

Hsi-Ming Lee ◽

Nicole Napolitano ◽

McKenzie Clemens ◽

Yazhou Zhang ◽

...

Keyword(s):

Proinflammatory Cytokines ◽

Inflammatory Mediators ◽

Mononuclear Cells ◽

Alveolar Bone ◽

Inflammatory Diseases ◽

Parent Compound ◽

Therapeutic Effects ◽

Chronic Inflammatory Diseases ◽

Periodontal Inflammation ◽

Increased Risk

Chronic inflammatory diseases such as periodontitis have been associated with increased risk for various medical conditions including diabetes and cardiovascular disease. Endotoxin (lipopolysaccharide, LPS), derived from gram-negative periodonto-pathogens, can induce the local accumulation of mononuclear cells in the inflammatory lesion, increasing proinflammatory cytokines and matrix metalloproteinases (MMPs). This ultimately results in the destruction of periodontal connective tissues including alveolar bone. Curcumin is the principal dyestuff in the popular Indian spice turmeric and has significant regulatory effects on inflammatory mediators but is characterized by poor solubility and low bioactivity. Recently, we developed a series of chemically modified curcumins (CMCs) with increased solubility and zinc-binding activity, while retaining, or further enhancing, their therapeutic effects. In the current study, we demonstrate that a novel CMC (CMC 2.5: 4-methoxycarbonyl curcumin) has significant inhibitory effects, better than the parent compound curcumin, on proinflammatory cytokines and MMPs inin vitro, in cell culture, and in an animal model of periodontal inflammation. The therapeutic potential of CMC 2.5 and its congeners may help to prevent tissue damage during various chronic inflammatory diseases including periodontitis and may reduce the risks of systemic diseases associated with this local disorder.

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