Knockout of Dectin-1 does not modify disease onset or progression in a MATR3 S85C knock-in mouse model of ALS.

Microglia have been increasingly implicated in neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Dectin-1, encoded by the gene, is highly upregulated in a specific microglial response state called disease-associated microglia (DAM) in various neurodegenerative conditions. However, the role of Dectin-1 in ALS is undetermined.

Microglia and Astrocytes in Amyotrophic Lateral Sclerosis: Disease-Associated States, Pathological Roles, and Therapeutic Potential.

Microglial and astrocytic reactivity is a prominent feature of amyotrophic lateral sclerosis (ALS). Microglia and astrocytes have been increasingly appreciated to play pivotal roles in disease pathogenesis. These cells can adopt distinct states characterized by a specific molecular profile or function depending on the different contexts of development, health, aging, and disease.

Synthetic Strategies for Improving Solubility: Optimization of Novel Pyrazolo[1,5-]pyrimidine CFTR Activator That Ameliorates Dry Eye Disease.

Dry eye disease (DED) is one of the most prevalent ocular diseases but has limited treatment options. Cystic fibrosis transmembrane conductance regulator (CFTR), a major chloride channel that stimulates fluid secretion in the ocular surface, may pave the way for new therapeutic strategies for DED. Herein, we report the optimization of Cact-3, a potent CFTR activator with poor solubility, to , a potent CFTR activator with suitable solubility for eye drop formulation.

Selective Loss of MATR3 in Spinal Interneurons, Upper Motor Neurons and Hippocampal CA1 Neurons in a MATR3 S85C Knock-In Mouse Model of Amyotrophic Lateral Sclerosis.

The neuropathological hallmark of amyotrophic lateral sclerosis (ALS) is motor neuron degeneration in the spinal cord and cortex. Accumulating studies report that other neurons in the central nervous system (CNS) are also affected in ALS. Mutations in , which encodes a nuclear matrix protein involved in RNA splicing, have been linked to ALS.

Using Social Media Data to Understand Consumers' Information Needs and Emotions Regarding Cancer: Ontology-Based Data Analysis Study.

Background: Analysis of posts on social media is effective in investigating health information needs for disease management and identifying people's emotional status related to disease. An ontology is needed for semantic analysis of social media data.

Objective: This study was performed to develop a cancer ontology with terminology containing consumer terms and to analyze social media data to identify health information needs and emotions related to cancer.

Selective neuronal degeneration in MATR3 S85C knock-in mouse model of early-stage ALS.

A missense mutation, S85C, in the MATR3 gene is a genetic cause for amyotrophic lateral sclerosis (ALS). It is unclear how the S85C mutation affects MATR3 function and contributes to disease. Here, we develop a mouse model that harbors the S85C mutation in the endogenous Matr3 locus using the CRISPR/Cas9 system.

Understanding the Public's Emotions about Cancer: Analysis of Social Media Data.

Cancer survivors suffer from emotional distress, which varies depending on several factors. However, existing emotion management programs are insufficient and do not take into consideration all of the factors. Social media provides a platform for understanding the emotions of the public.

Knockdown of genes involved in axonal transport enhances the toxicity of human neuromuscular disease-linked MATR3 mutations in Drosophila.

Mutations in the nuclear matrix protein Matrin 3 (MATR3) have been identified in amyotrophic lateral sclerosis and myopathy. To investigate the mechanisms underlying MATR3 mutations in neuromuscular diseases and efficiently screen for modifiers of MATR3 toxicity, we generated transgenic MATR3 flies. Our findings indicate that expression of wild-type or mutant MATR3 in motor neurons reduces climbing ability and lifespan of flies, while their expression in indirect flight muscles (IFM) results in abnormal wing positioning and muscle degeneration.

Tyrosinase-Targeting Gallacetophenone Inhibits Melanogenesis in Melanocytes and Human Skin-Equivalents.

Demands for safe depigmentation compounds are constantly increasing in the pharmaceutical and cosmetic industry, since the numerous relevant compounds reported to date have shown undesirable side effects or low anti-melanogenic effects. In this study, we reported three novel inhibitors of tyrosinase, which is the key enzyme in melanogenesis, identified using docking-based high throughput virtual screening of an in-house natural compound library followed by mushroom tyrosinase inhibition assay. Of the three compounds, gallacetophenone showed high anti-melanogenic effect in both human epidermal melanocytes and a 3D human skin model, MelanoDerm.

Novel tacrine-pyridinium hybrid reactivators of organophosphorus-inhibited acetylcholinesterase: Synthesis, molecular docking, and in vitro reactivation study.

First-line medical treatment against nerve agents consists of co-administration of anticholinergic agents and oxime reactivators, which reactivate inhibited AChE. Pralidoxime, a commonly used oxime reactivator, is effective against some nerve agents but not against others; thus, new oxime reactivators are needed. Novel tacrine-pyridinium hybrid reactivators in which 4-pyridinealdoxime derivatives are connected to tacrine moieties by linear carbon chains of different lengths (C2-C7) were prepared (Scheme 1, 5a-f).

A novel anti-melanogenic agent, KDZ-001, inhibits tyrosinase enzymatic activity.

Background: The demand for anti-melanogenic agents is increasing due to the unwanted side effects of current treatments. To find an effective anti-melanogenic agent, we used zebrafish as a whole animal model for phenotype-based drug and cosmetic discovery screening.

Objectives: The aim of this study was to identify and explore a small molecule that could be used for skin-whitening cosmetics.

Discovery of novel [1,2,4]triazolo[4,3-a]quinoxaline aminophenyl derivatives as BET inhibitors for cancer treatment.

Bromodomain and extra-terminal (BET) proteins, a class of epigenetic reader domains has emerged as a promising new target class for small molecule drug discovery for the treatment of cancer, inflammatory, and autoimmune diseases. Starting from in silico screening campaign, herein we report the discovery of novel BET inhibitors based on [1,2,4]triazolo[4,3-a]quinoxaline scaffold and their biological evaluation. The hit compound was optimized using the medicinal chemistry approach to the lead compound with excellent inhibitory activities against BRD4 in the binding assay.

A Phase I study of cabazitaxel in patients with advanced gastric cancer who have failed prior chemotherapy (GASTANA).

Purpose: This Phase I dose-escalation study (GASTANA) evaluated the safety, tolerability, pharmacokinetics and preliminary antitumor activity of cabazitaxel in Asian patients with advanced gastric adenocarcinoma failing two prior chemotherapy regimens.

Methods: Cabazitaxel safety/tolerability was determined using a standard 3 + 3 dose-escalation design based on dose-limiting toxicities (DLTs) in Cycle 1. Three dose levels (DL) were planned: 20, 25 and 15 mg/m(2) (DL 1, DL 2 and DL -1).

Are patients with POEMS syndrome at increased risk of Salmonella aortitis?

We report a case of Salmonella infectious aortitis in a patient with POEMS (peripheral neuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome, possibly indicating that vasculopathy associated with POEMS syndrome may increase the risk of Salmonella endovascular infection.

Pharmacodynamics of doxycycline for chemoprophylaxis of Lyme disease: preliminary findings and possible implications for other antimicrobials.

The purpose of this study was to begin to characterise the pharmacodynamic parameters of single-dose doxycycline for the prevention of Lyme disease following a tick bite. Based on limited data from published human and murine studies, it was found that there is a direct correlation between efficacy rate and the area under the time-concentration of free antibiotic curve divided by the minimum inhibitory concentration (fAUC/MIC) (R(2)=0.74, using Pearson correlation), but not the maximum concentration of free drug in serum divided by the MIC (fC(max)/MIC) or the time that the free drug concentration remains above the MIC (fT>MIC).

Conversion of intermittent exotropia types subsequent to part-time occlusion therapy and its sustainability.

Purpose: To evaluate the effects of part-time occlusion therapy on types of intermittent exotropia and sustainability of converted types.

Methods: Forty-four and 26 children with basic-type and convergence-insufficiency-type intermittent exotropia, respectively, were evaluated in this study. Upon initial examination, we obtained both distant and near deviating angles using prism cover tests, after correcting for refractive errors.

Primary facial skin cancer: clinical characteristics and surgical outcome in Chungbuk Province, Korea.

Clinical features of facial skin cancer in Asian population including Korean are not readily available. In the present study, we analyzed the clinical characteristics and the surgical results of primary facial skin cancer in Chungbuk Province, Korea. Eighty-six cases of primary facial skin cancer collected during a 10-yr period (1994-2003) were retrospectively reviewed about the clinical characteristics including age, sex, annual diagnostic rate, types of tumor, specific sites of occurrence, and the surgical results.

Association of right ventricular dilatation with bilateral pulmonary embolism, pulmonary embolism in a main pulmonary artery and lobar, segmental and subsegmental pulmonary embolism in 190 patients with acute pulmonary embolism.

Background: Acute pulmonary embolism (PE) may result in right ventricular (RV) pressure overload with a dilated RV which can be diagnosed by two-dimensional echocardiography.

Methods: A retrospective analysis was performed in 190 unselected patients who had acute PE documented by contrast-enhanced spiral computed tomographic scanning. The 190 patients included 104 women and 86 men, mean age 58 +/- 15 years.

Association of right ventricular dysfunction with in-hospital mortality in patients with acute pulmonary embolism and reduction in mortality in patients with right ventricular dysfunction by pulmonary embolectomy.

Twenty-one of 64 patients (33%) with pulmonary embolisms with right ventricular (RV) dilation and 6 of 126 patients (5%) with pulmonary embolisms without RV dilation died during hospitalization (p <0.001). In the 64 patients with RV dilation, in-hospital mortality occurred in 2 of 18 hemodynamically unstable patients (11%) who underwent pulmonary embolectomy, in 2 of 6 hemodynamically stable patients (33%) treated with thrombolytic therapy plus intravenous heparin, and in 17 of 40 hemodynamically stable patients (43%) treated with intravenous heparin (p <0.