Substance P regulates memory Th17 cell generation and maintenance in chronic dry eye disease.

Substance P is a neuropeptide expressed by nerves and an array of cells that serves as a critical mediator of neuroinflammation. Our recent work has demonstrated that blocking the preferred receptor for substance P, neurokinin 1 receptor, effectively suppresses the induction of acute dry eye disease by preserving regulatory T-cell function, while inhibiting antigen-presenting cell maturation and subsequent generation of effector Th17 cells. Clinically, dry eye disease is a chronic disorder characterized by sustained ocular surface inflammation, which is mediated by long-lived memory Th17 cells demonstrated in our well-established chronic dry eye disease model.

Developing deprotectase biocatalysts for synthesis.

Organic synthesis often requires multiple steps where a functional group (FG) is concealed from reaction by a protecting group (PG). Common PGs include -carbobenzyloxy (Cbz or Z) of amines and -butyloxycarbonyl (OBu) of acids. An essential step is the removal of the PG, but this often requires excess reagents, extensive time and can have low % yield.

Myeloid-derived suppressor cells promote allograft survival by suppressing regulatory T cell dysfunction in high-risk corneal transplantation.

Highly inflamed and neovascularized corneal graft beds are known as high-risk (HR) environments for transplant survival. One of the primary factors leading to this rejection is reduction in the suppressive function of regulatory T cells (Treg). Our results show that myeloid-derived suppressor cells (MDSC) counteract interleukin-6-mediated Treg dysfunction by expressing interleukin-10.

The Neuropeptide α-Melanocyte-Stimulating Hormone Prevents Persistent Corneal Edema following Injury.

Corneal endothelial cells (CEnCs) regulate corneal hydration and maintain tissue transparency through their barrier and pump function. However, these cells exhibit limited regenerative capacity following injury. Currently, corneal transplantation is the only established therapy for restoring endothelial function, and there are no pharmacologic interventions available for restoring endothelial function.

The impact of donor diabetes on corneal transplant immunity.

Corneal transplantation is the most common form of solid tissue grafting, with an approximately 80% to 90% success rate. However, success rates may decline when donor tissues are derived from patients with a history of diabetes mellitus (DM). To evaluate the underlying immunopathologic processes that cause graft rejection, we used streptozotocin-induced type 1 DM (DM1) and transgenic Lep type 2 DM (DM2) diabetic murine models as donors and nondiabetic BALB/c as recipients.

Long-lived autoreactive memory CD4 T cells mediate the sustained retinopathy in chronic autoimmune uveitis.

Chronic uveitis comprises heterogeneous clinical entities characterized by sustained and recurrent intraocular inflammation that is believed to be driven by autoimmune responses. The management of chronic uveitis is challenging with the limited availability of efficacious treatments, and the underlying mechanisms mediating disease chronicity remain poorly understood as the majority of experimental data are derived from the acute phase of the disease (the first 2-3 weeks post-induction). Herein, we investigated the key cellular mechanisms underlying chronic intraocular inflammation using our recently established murine model of chronic autoimmune uveitis.

Modulating the tachykinin: Role of substance P and neurokinin receptor expression in ocular surface disorders.

Substance P (SP) is a tachykinin expressed by various cells in the nervous and immune systems. SP is predominantly released by neurons and exerts its biological and immunological effects through the neurokinin receptors, primarily the neurokinin-1 receptor (NK1R). SP is essential for maintaining ocular surface homeostasis, and its reduced levels in disorders like diabetic neuropathy disrupt the corneal tissue.

BioWF: A Naturally-Fused, Di-Domain Biocatalyst from Biotin Biosynthesis Displays an Unexpectedly Broad Substrate Scope.

The carbon backbone of biotin is constructed from the C di-acid pimelate, which is converted to an acyl-CoA thioester by an ATP-dependent, pimeloyl-CoA synthetase (PCAS, encoded by BioW). The acyl-thioester is condensed with ʟ-alanine in a decarboxylative, Claisen-like reaction to form an aminoketone (8-amino-7-oxononanoic acid, AON). This step is catalysed by the pyridoxal 5'-phosphate (PLP)-dependent enzyme (AON synthase, AONS, encoded by BioF).

Autoreactive memory Th17 cells are principally derived from T-betRORγt Th17/1 effectors.

Effector Th17 cells, including IFN-γIL-17 (eTh17) and IFN-γIL-17 (eTh17/1) subsets, play critical pathogenic functions in the induction of autoimmunity. As acute inflammation subsides, a small proportion of the effectors survive and convert to memory Th17 cells (mTh17), which sustain chronic inflammation in autoimmune diseases. Herein, we investigated the differential contributions of eTh17 versus eTh17/1 to the memory pool using an experimental model of ocular autoimmune disease.

Effectiveness of Neuromuscular Electrical Stimulation and Dynamic Mobilization Exercises on Equine Multifidus Muscle Cross-Sectional Area.

Equine back pain can potentially initiate an unstable intervertebral situation that results in atrophy and dysfunction of the epaxial muscles even after back pain has resolved. Several physiotherapy approaches are advocated to promote the strengthening of the multifidus muscle. This study aimed to asses and compare the effect of dynamic mobilization exercises (DME) and neuromuscular electrical stimulation (NMES) in 8 adult horses (4 individuals by group) to increase the cross-sectional area (CSA) of this muscle after a 7-weeks period treatment.

Role of the Phospholipase C Pathway and Calcium Mobilization in Oxytocin-Induced Contraction of Lacrimal Gland Myoepithelial Cells.

Purpose: We reported that oxytocin (OXT), added to freshly prepared lacrimal gland lobules, induced myoepithelial cell (MEC) contraction. In other systems, OXT activates phospholipase C (PLC) generating Inositol 1,4,5-trisphosphate (IP3) which increases intracellular calcium concentration ([Ca2+]i) causing contraction. The aim of the current study was to investigate the role of this pathway in OXT-induced contraction of MEC.

The Neuropeptide Alpha-Melanocyte-Stimulating Hormone Is Critical for Corneal Endothelial Cell Protection and Graft Survival after Transplantation.

Corneal transplantation is the most common form of tissue transplantation. The success of corneal transplantation mainly relies on the integrity of corneal endothelial cells (CEnCs), which maintain tissue transparency by pumping out excess water from the cornea. After transplantation, the rate of CEnC loss far exceeds that seen with normal aging, which can threaten sight.

Evidence of Spread of Bemisia tabaci (Hemiptera: Aleyrodidae) Mediated by Internal Transportation of Ornamental Plants in Brazil.

Two Bemisia tabaci (Gennadius) species, Middle East-Asia Minor 1 (MEAM1) and Mediterranean (MED), are major pests that are dispersed throughout the world. While MEAM1 was introduced in Brazil in the 1990s, MED was reported recently with limited spread. Here, a survey was performed to examine whether MED whiteflies are widely present in the Federal District region, in central Brazil.

Effect of Dry Eye Disease on the Kinetics of Lacrimal Gland Dendritic Cells as Visualized by Intravital Multi-Photon Microscopy.

The lacrimal gland (LG) is the main source of the tear film aqueous layer and its dysfunction results in dry eye disease (DED), a chronic immune-mediated disorder of the ocular surface. The desiccating stress (DS) murine model that mimics human DED, results in LG dysfunction, immune cell infiltration, and consequently insufficient tear production. To date, the immune cell kinetics in DED are poorly understood.

Topical Adoptive Transfer of Plasmacytoid Dendritic Cells for Corneal Wound Healing.

Plasmacytoid dendritic cells (pDCs) are crucial for corneal homeostasis through secretion of various anti-angiogenic molecules and growth factors. Due to its avascular nature, only a limited number of adoptively transferred cells home to the cornea, when administered systemically. In addition, local adoptive transfer of cells poses several challenges and the clinical application of commonly used techniques is limited.

Impact of MRI Selection on Triage of Endovascular Therapy in Acute Ischemic Stroke: The MRI in Acute Management of Ischemic Stroke (MIAMIS) Registry.

Background: The recently published multicenter randomized DAWN trial confirmed greater outcome benefit of endovascular therapy (ET) for anterior circulation large vessel occlusion ischemic stroke from 6 to 24 h from symptom onset compared to medical management in patients selected by advanced imaging with MRI or perfusion CT to identify mismatch between clinical deficit and infarct volume, which represents salvageable penumbra. The debate of CT over MRI is usually the potentially increase time consumption and the difficulty in establishing an adequate standardized workflow utilizing MRI during the hyperacute phase.

Purpose: While CT-based selection of patients is the current standard of care, we sought to determine the time impact of the alternative approach of MRI selection in the 0-12 h window.

Intravital Multiphoton Microscopy of the Ocular Surface: Alterations in Conventional Dendritic Cell Morphology and Kinetics in Dry Eye Disease.

Dry eye disease (DED) is a multifactorial disease of the ocular surface, characterized by loss of tear film homeostasis and ocular symptoms, in which neurosensory abnormalities have recently been shown to play an etiological role. Although the role of inflammation has been widely studied in DED, the kinetics of immune cells of the ocular surface in this complex disease are hereto unclear. Herein, we utilized intravital multiphoton imaging on transgenic mice to investigate the 3D morphology and kinetics of conventional dendritic cells (cDCs) and the role of ocular surface sensory nerves in regulating them in both the naïve state and experimental DED.

Multiphoton Intravital Microscopy of Mandibular Draining Lymph Nodes: A Mouse Model to Study Corneal Immune Responses.

Multiphoton intravital microscopy (MP-IVM) is a powerful tool to image cells . Its application in immunology research has opened new horizons, allowing intravital imaging of leukocytes at the single-cell level. A transparent cornea is vital to retain vision.

Elucidating the mechanism of action of alpha-1-antitrypsin using retinal pigment epithelium cells exposed to high glucose. Potential use in diabetic retinopathy.

Background: Alpha-1-antitrypsin is a protein involved in avoidance of different processes that are seen in diabetic retinopathy pathogenesis. These processes include apoptosis, extracellular matrix remodeling and damage of vessel walls and capillaries. Furthermore, because of its anti-inflammatory effects, alpha-1-antitrypsin has been proposed as a possible therapeutic approach for diabetic retinopathy.

Alpha-1-antitrypsin ameliorates inflammation and neurodegeneration in the diabetic mouse retina.

Diabetic retinopathy (DR) is the most common cause of blindness in the working age population. Early events of DR are accompanied by neurodegeneration of the inner retina resulting in ganglion cell loss. These findings together with reduced retinal thickness are observed within the first weeks of experimental DR.

Possible neuroprotective role of P2X2 in the retina of diabetic rats.

Background: Purinergic receptors are expressed in different tissues including the retina. These receptors are involved in processes like cell growth, proliferation, activation and survival. ATP is the major activator of P2 receptors.

Corneal Neovascularization: A Combined Approach of Bevacizumab and Suramin Showed Increased Antiangiogenic Effect Through Downregulation of BFGF and PX.

Purpose: The objective is to analyze the antiangiogenic mechanism of suramab, a pharmaceutical compound of bevacizumab and suramin, in a rabbit model of corneal angiogenesis.

Material And Methods: Corneal neovascularization was induced in four groups of six New Zealand White rabbits by applying a filter paper disk soaked in 1 M Na (OH) on the central cornea. Group one was treated after injury with intravenous suramab at a dose equivalent to 3 mg/kg of bevacizumab and 10 mg/kg of suramin.