a b s t r a c tThe discovery of the TLRs family and more precisely its functions opened a variety of gates to modulate immunological host responses. TLRs 7/8 are located in the endosomal compartment and activate a specific signaling pathway in a MyD88-dependant manner. According to their involvement into various autoimmune, inflammatory and malignant diseases, researchers have designed diverse TLRs 7/8 ligands able to boost or block the inherent signal transduction. These modulators are often small synthetic compounds and most act as agonists and to a much lesser extent as antagonists. Some of them have reached preclinical and clinical trials, and only one has been approved by the FDA and EMA, imiquimod. The key to the success of these modulators probably lies in their combination with other therapies as recently demonstrated. We gather in this review more than 360 scientific publications, reviews and patents, relating the extensive work carried out by researchers on the design of TLRs 7/8 modulators, which are classified firstly by their biological activities (agonist or antagonist) and then by their chemical structures, which total syntheses are not discussed here. This review also reports about 90 clinical cases, thereby showing the biological interest of these modulators in multiple pathologies.

Background Prevalence and distribution of oral mucosal lesions in a sample of Lebanese population attending the School of Dentistry of Lebanese University is necessary to evaluate their oral health situation. Objectives The aim of the present study was to determine the prevalence and distribution of oral mucosal lesions of patients attending the School of Dentistry. Methods A descriptive study was carried out by retrospectively examining a total of 231 medical and clinical examination record files of patients, attending the School of Dentistry Lebanese University for multidisciplinary dental treatments. 178 medical records were retained. Each medical and clinical examination record was done by an undergraduate student and then evaluated by a doctor. The record file included a civil status, chief complaint, medical history, and extraoral and intraoral clinical examination during the period between October 2014 and May 2015. Exclusion criteria were lack of written information in their medical and clinical examination record and being nonevaluated by a doctor. Data regarding age, gender, socioeconomic status, chief complaint, systemic diseases, and drugs intake were collected by using a questionnaire while the type of extraoral and oral mucosal lesions by clinical examination. Results The sample consisted of 102 (57.3%) females and 76 (42.7%) males. The age ranged from 10 to 92 years with a mean age of 40.1 years. Among these subjects, 110 (61.8%) presented with one or more lesions. All patients were Lebanese. The most common lesion diagnosed was coated/hairy tongue affecting 17.4% of the subjects, followed by melanotic macule (11.2%), gingivitis (9.6), linea alba (6.2%), tongue depapillation (5.1), leukoplakia (5.1), traumatic fibroma (4.5), frictional keratosis (3.9%), fissured tongue (3.9%), hemangiomas (3.9%), Fordyce granules (3.9%), dry mucosa (3.4), angular cheilitis (2.2), gingival hyperplasia (2.2), and crenulated tongue (1.7%). Overall, the prevalence of oral mucosal lesions did not significantly differ between sex and age groups. Conclusions The high prevalence of oral mucosal lesions necessitates adequate awareness and management of these lesions in the general population. Dental clinicians should be knowledgeable and familiar with the etiopathogenesis, clinical presentation, diagnosis, and management of these lesions.

The Toll-like receptors (TLRs) 7 and 8 play an important role in the immune system activation, and their agonists may therefore serve as promising candidate vaccine adjuvants. However, the chronic immune activation by excessive TLR stimulation is a hallmark of several clinically important infectious and autoimmune diseases, which warrants the search for TLR antagonists. In this study, we have synthesized and characterized a variety of compounds belonging to three heterocyclic chemical series: imidazo­[1,2-a]­pyrazine, imidazo­[1,5-a]­quinoxaline, and pyrazolo­[1,5-a]­quinoxaline. These compounds have been tested for their TLR7 or TLR8 agonistic and antagonistic activities. Several of them are shown to be selective TLR7 antagonists without any TLR7 or TLR8 agonistic activity. The selectivity was confirmed by a comparative ligand-docking study in TLR7 antagonist pocket. Two compounds of the pyrazolo­[1,5-a]­quinoxaline series (10a and 10b) are potent selective TLR7 antagonists and may be considered as promising starting points for the development of new therapeutic agents.

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