Atropisomerism Observed in Galactose-Based Monosaccharide Inhibitors of Galectin-3 Comprising 2-Methyl-4-phenyl-2,4-dihydro-3-1,2,4-triazole-3-thione.

Galectin-3 (Gal-3) is a carbohydrate binding protein that has been implicated in the development and progression of fibrotic diseases. Proof-of-principal animal models have demonstrated that inhibition of Gal-3 is a potentially viable pathway for the treatment of fibrosis─with small molecule Gal-3 inhibitors advanced into clinical trials. We hereby report the discovery of novel galactose-based monosaccharide Gal-3 inhibitors comprising 2-methyl-4-phenyl-2,4-dihydro-3-1,2,4-triazole-3-thione (compound ) and 4-phenyl-4-1,2,4-triazole (compound ).

Parotid saliva and blood biomarkers in juvenile idiopathic arthritis in relation to temporomandibular joint magnetic resonance imaging findings.

Background: Juvenile idiopathic arthritis (JIA) often affects the temporomandibular joint (TMJ) caused by an abnormal immune system that includes overactive inflammatory processes. Salivary biomarkers may be a powerful tool that can help establishing diagnosis, prognosis and monitor disease progress.

Objective: The objective was to investigate biomarkers in parotid saliva and blood plasma in relation to temporomandibular joint (TMJ) magnetic resonance imaging (MRI) findings in patients with JIA and healthy individuals.

Evaluating the native oxide of titanium as an electrocatalyst for oxalic acid reduction.

Herein, we show that unmodified titanium electrodes bearing the naturally-forming native TiO coating display superior activity for the electroreduction of oxalic acid to glyoxylic acid and glycolic acid compared to Ti-based electrodes that have been deliberately modified for this purpose, in terms of both oxalic acid conversion and overall yields of reduced products.

Identification of benzothiazole derived monosaccharides as potent, selective, and orally bioavailable inhibitors of human and mouse galectin-3; a rare example of using a S···O binding interaction for drug design.

As a result of our continued efforts to pursue Gal-3 inhibitors that could be used to fully evaluate the potential of Gal-3 as a therapeutic target, two novel series of benzothiazole derived monosaccharides as potent (against both human and mouse Gal-3) and orally bioavailable Gal-3 inhibitors, represented by 4 and 5, respectively, were identified. These discoveries were made based on proposals that the benzothiazole sulfur atom could interact with the carbonyl oxygen of G182/G196 in h/mGal-3, and that the anomeric triazole moiety could be modified into an N-methyl carboxamide functionality. The interaction between the benzothiazole sulfur and the carbonyl oxygen of G196 in mGal-3 was confirmed by an X-ray co-crystal structure of early lead 9, providing a rare example of using a S···O binding interaction for drug design.

Retraction: Synthesis of a chiral dinuclear Cu(II)-benzothiazolamine complex: evidence of cuprophilic interaction in its structure and exploration of its electrochemical properties and catalytic performance.

Retraction of 'Synthesis of a chiral dinuclear Cu(II)-benzothiazolamine complex: evidence of cuprophilic interaction in its structure and exploration of its electrochemical properties and catalytic performance' by O. Stephen Ojo , , 2024, https://doi.org/10.

Synthesis of a chiral dinuclear Cu(II)-benzothiazolamine complex: evidence of cuprophilic interaction in its structure and exploration of its electrochemical properties and catalytic performance.

The synthesis of a chiral dinuclear [Cu(OAc)(L1)] complex (A) and its analogues Cu(OAc)(L1) (B), Cu(OAc)(L1)PPh (C), CuBr(L1)PPh (D), and Cu(OAc)(L2) (E) is described. The X-ray structure of A reveals a cuprophilic interaction (2.65 Å) and shows that L1 behaves as a monodentate ligand.

Juvenile idiopathic arthritis and the temporomandibular joint: a case-control study of magnetic resonance imaging findings in relation to clinical and psychosocial factors.

Aim: In juvenile idiopathic arthritis (JIA), the temporomandibular joint (TMJ) is a particularly challenging joint to assess both clinically and with imaging. The aim of this article is to investigate TMJ magnetic resonance imaging (MRI) findings in relation to clinical and psychosocial factors in patients with JIA and healthy individuals related to TMJ arthritis in JIA.

Materials: In total, 45 patients (6-16 years) with JIA and 16 healthy age- and sex-matched controls were examined according to the diagnostic criteria for temporomandibular disorders (DC/TMD).

Molecular mechanism of interspecies differences in the binding affinity of TD139 to Galectin-3.

Galectin-3 (Gal-3), a β-galactoside-binding lectin, has been implicated in a plethora of pathological disorders including fibrosis, inflammation, cancer and metabolic diseases. TD139-a thio-digalactoside inhibitor developed by Galecto Biotech as a potential therapeutic for idiopathic pulmonary fibrosis-is the most advanced small-molecule Gal-3 inhibitor in clinical studies. It binds to human Gal-3 with high affinity but has lower affinity towards mouse and rat homologs, which is also manifested in the differential inhibition of Gal-3 function.

Synthesis, Structure-Activity Relationships, and In Vivo Evaluation of Novel Tetrahydropyran-Based Thiodisaccharide Mimics as Galectin-3 Inhibitors.

Galectin-3 is a member of a family of β-galactoside-binding proteins. A substantial body of literature reports that galectin-3 plays important roles in cancer, inflammation, and fibrosis. Small-molecule galectin-3 inhibitors, which are generally lactose or galactose-based derivatives, have the potential to be valuable disease-modifying agents.

On the role of the frontal projection in videoradiography of velopharynx in decision-making for a velopharyngeal flap plasty in patients with cleft palate.

Despite uneventful primary surgery, patients with cleft palate may experience velopharyngeal insufficiency (VPI) and hypernasal speech. Videoradiography of velopharynx is a commonly used method to visualize velopharyngeal function and a velopharyngeal flap is often used to counteract VPI. The aim of this study was to investigate whether the frontal projection on videoradiography plays a role in the decision-making about velopharyngeal flap surgery, or possibly the width and orientation of the flap.

Anterior approach of abdominal field block at linea semilunaris: A surgically assisted novel technique for postoperative analgesia in cesarean section.

Context: Post Caesarean pain is described as moderate to severe. Although advances in the new analgesics techniques, no current standard exists for optimizing and managing. Taking into consideration of acute post Caesarean pain, this novel technique of surgically assisted anterior abdominal field block at linea semilunaris have proved considerable analgesic potential along with multimodal analgesia.

Modulation of K 11.1 (hERG) channels by 5-(((1H-indazol-5-yl)oxy)methyl)-N-(4-(trifluoromethoxy)phenyl)pyrimidin-2-amine (ITP-2), a novel small molecule activator.

Background And Purpose: Activators of K 11.1 (hERG) channels have potential utility in the treatment of acquired and congenital long QT (LQT) syndrome. Here, we describe a new hERG channel activator, 5-(((1H-indazol-5-yl)oxy)methyl)-N-(4-(trifluoromethoxy)phenyl)pyrimidin-2-amine (ITP-2), with a chemical structure distinct from previously reported compounds.

Selective I Inhibitors for the Potential Treatment of Atrial Fibrillation: Optimization of the Phenyl Quinazoline Series Leading to Clinical Candidate 5-[5-Phenyl-4-(pyridin-2-ylmethylamino)quinazolin-2-yl]pyridine-3-sulfonamide.

We have recently disclosed 5-phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine 1 as a potent I current blocker with selectivity versus hERG, Na and Ca channels, and an acceptable preclinical PK profile. Upon further characterization in vivo, compound 1 demonstrated an unacceptable level of brain penetration. In an effort to reduce the level of brain penetration while maintaining the overall profile, SAR was developed at the C2' position for a series of close analogues by employing hydrogen bond donors.

Discovery of 5-Phenyl-N-(pyridin-2-ylmethyl)-2-(pyrimidin-5-yl)quinazolin-4-amine as a Potent I Kur Inhibitor.

A new series of phenylquinazoline inhibitors of Kv 1.5 is disclosed. The series was optimized for Kv 1.

Signs and symptoms of TMJ disorders in adults after adolescent Herbst therapy: a 6-year and 32-year radiographic and clinical follow-up study.

Objective: To analyze radiographic signs of temperomandibular joint (TMJ) osteoarthritis and clinical TMJ symptoms in patients 6 years and 32 years after treatment with a Herbst appliance.

Materials And Methods: Fourteen patients were derived from a sample of 22 with Class II division 1 malocclusions consecutively treated with a banded Herbst appliance at the age of 12-14 years old (T1-T2). The subjects were reexamined after therapy at the ages of 20 years (T3) and 46 years (T4).

Effective dose of cone beam CT (CBCT) of the facial skeleton: a systematic review.

Objective: To estimate effective dose of cone beam CT (CBCT) of the facial skeleton with focus on measurement methods and scanning protocols.

Methods: A systematic review, which adhered to the preferred reporting items for systematic reviews (PRISMA) Statement, of the literature up to April 2014 was conducted. Data sources included MEDLINE®, The Cochrane Library and Web of Science.

A 15-year follow-up of temporomandibular joint symptoms and magnetic resonance imaging findings in whiplash patients: a prospective, controlled study.

Objective: This study aimed to determine the incidence, prevalence, and progression of temporomandibular joint (TMJ) magnetic resonance (MR) imaging findings and symptoms in patients over a 15-year period after whiplash trauma, compared with control participants.

Study Design: Sixty consecutive patients were enrolled directly after whiplash trauma. The study protocol included TMJ MR imaging at inception and 15 years later, as well as a questionnaire and interview at inception, at 1-year follow-up, and at 15-year follow-up.

Temporomandibular joints in asymptomatic and symptomatic nonpatient volunteers: a prospective 15-year follow-up clinical and MR imaging study.

Purpose: To determine the incidence, prevalence, and progression of temporomandibular joint (TMJ) magnetic resonance (MR) imaging findings and symptoms during 15 years in adult asymptomatic and symptomatic volunteers (nonpatients).

Materials And Methods: A regional committee for medical research ethics approved the study, and informed volunteer consent was obtained. Fifty-three volunteers were examined at study inception.

"I'll never forget this": evaluating a pilot workshop in effective communication for dental students.

This study evaluated a pilot workshop for teaching communication skills to dental students. The methodology is based on an experiential learning approach, the use of realistic clinical scenarios, simulated patients, and an integrated teaching team of both educational researchers and dentists. Furthermore, the methodology was adapted for short workshops, which is thought to offer better possibilities for frequent and effective training of communication skills throughout the curriculum.

Accuracy of patients' recall of temporomandibular joint pain and dysfunction after experiencing whiplash trauma: a prospective study.

Background: Researchers have conducted studies regarding whiplash-induced temporomandibular joint (TMJ) pain and dysfunction mainly under the presumption that patients' memory of symptoms remains accurate across time. In this prospective study, the authors aimed to determine the frequency of patients' inaccurate retrospective reports of TMJ pain and dysfunction after whiplash trauma.

Methods: The authors assessed TMJ pain and dysfunction in 60 patients consecutively seen in a hospital emergency department directly after the patients experienced whiplash trauma in rear-end automobile accidents.

Estimation of binding rate constants using a simultaneous mixed-effects method: application to monoamine transporter reuptake inhibitor reboxetine.

Background And Purpose: Reboxetine is a clinically used antidepressant and is a racemic mixture of two enantiomers, SS- and RR-reboxetine. The aim of the work described in this manuscript was to determine the kinetics of binding of the RR- and SS-reboxetine to the human noradrenaline transporter (hNET).

Experimental Approach: We have applied a simultaneous mixed-effects method to the analysis of the transient kinetics of binding of SS-, RR- and racemic reboxetine to hNET.

A Drosophila behavioral mutant, down and out (dao), is defective in an essential regulator of Erg potassium channels.

To signal properly, excitable cells must establish and maintain the correct balance of various types of ion channels that increase or decrease membrane excitability. The mechanisms by which this balance is regulated remain largely unknown. Here, we describe a regulatory mechanism uncovered by a Drosophila behavioral mutant, down and out (dao).

The effect of heat stress on the antibacterial resistance and plasmid profile in Escherichia coli isolates.

In order to study the effect of heat stress on the antibacterial resistance and plasmid profile in Escherichia coli, thirty E. coli were isolated from sheep liver. Antibiotic susceptibility test were done by antibiotic disc diffusion method using filter paper disc on two 24 h cultures of each isolate which grown at 37 and 43 degrees C simultaneously in BHI Broth (Merck VM460193 531).

Physiological properties of hERG 1a/1b heteromeric currents and a hERG 1b-specific mutation associated with Long-QT syndrome.

Cardiac I Kr is a critical repolarizing current in the heart and a target for inherited and acquired long-QT syndrome (LQTS). Biochemical and functional studies have demonstrated that I Kr channels are heteromers composed of both hERG 1a and 1b subunits, yet our current understanding of I Kr functional properties derives primarily from studies of homooligomers of the original hERG 1a isolate. Here, we examine currents produced by hERG 1a and 1a/1b channels expressed in HEK-293 cells at near-physiological temperatures.