Altered RNA editing has been linked to several neurodevelopmental disorders, including autism spectrum disorder (ASD) and intellectual disability, in addition to depression, schizophrenia, some cancers, viral infections and autoimmune disorders. The human ADAR2 is a potential therapeutic target for managing these various disorders due to its crucial role in adenosine to inosine editing. This study applied consensus scoring to rank potential ADAR2 inhibitors after performing molecular docking with AutoDock Vina and Glide (Maestro), using a library of 35,161 compounds obtained from traditional Chinese medicine. A total of 47 compounds were predicted to be good binders of the human ADAR2 and had insignificant toxicity concerns. Molecular dynamics (MD) simulations, including the molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) procedure, also emphasized the binding of the shortlisted compounds. The potential compounds had plausible binding free energies ranging from −81.304 to −1068.26 kJ/mol from the MM/PBSA calculations. ZINC000085511995, a naphthoquinone had more negative binding free energy (−1068.26 kJ/mol) than inositol hexakisphosphate (IHP) [−873.873 kJ/mol], an agonist and a strong binder of ADAR2. The potential displacement of IHP by ZINC000085511995 in the IHP binding site of ADAR2 could be explored for possible deactivation of ADAR2. Bayesian-based biological activity prediction corroborates the neuropharmacological, antineoplastic and antiviral activity of the potential lead compounds. All the potential lead compounds, except ZINC000014612330 and ZINC000013462928, were predicted to be inhibitors of various deaminases. The potential lead compounds also had probability of activity (Pa) > 0.442 and probability of inactivity (Pi) < 0.116 values for treating acute neurologic disorders, except for ZINC000085996580 and ZINC000013462928. Pursuing these compounds for their anti-ADAR2 activities holds a promising future, especially against neurological disorders, some cancers and viral infections caused by RNA viruses. Molecular interaction, hydrogen bond and per-residue decomposition analyses predicted Arg400, Arg401, Lys519, Trp687, Glu689, and Lys690 as hot-spot residues in the ADAR2 IHP binding site. Most of the top compounds were observed to have naphthoquinone, indole, furanocoumarin or benzofuran moieties. Serotonin and tryptophan, which are beneficial in digestive regulation, improving sleep cycle and mood, are indole derivatives. These chemical series may have the potential to treat neurological disorders, prion diseases, some cancers, specific viral infections, metabolic disorders and eating disorders through the disruption of ADAR2 pathways. A total of nine potential lead compounds were shortlisted as plausible modulators of ADAR2.
Of 586 employed patients with a whiplash injury 40 (7%) did not return to work. The risk was increased by three times in heavy manual workers, two and a half times in patients with prior psychological symptoms and doubled for each increase of grade of disability. The length of time off work doubled in patients with a psychological history and trebled for each increase in grade of disability. The self-employed were half as likely to take time off work, but recovered significantly more slowly than employees.
A rare chronic granulomatous disease is Rhinosporidiosis characterized by polypoidal lesions of mucus membrane .Commonly affected area are nose, conjunctiva, naso-pharynx and palate. The causative agent is rhinosporidium seeberi.The disease has been reported in 70 countries. It is prevalent in Indian subcontinent and endemic in Sri Lanka and India. We hereby present a case of 60 years old male native of Uttar Pradesh,eastern zone of India with recurrent polypoidal nasal rhinosporidosis. Patient presented with long standing history of nasal obstruction and intermittent epistaxis for three years. Diagnosis was confirmed by histopathological examination and was treated by complete surgical excision .This was a very unusual cause of nasal mass in our setting. Nasal rhinosporidiosis lesion may largely mimic other nasal polyps, therefore it is a message for clinicians to consider Rhinosporidiosis as differential diagnosis for patients presenting with nasal mass or swelling Tablet dapsone is effective to reduce recurrence. Laser technique is very new tool and quiet safe for removal of nasal rhinosporidiosis and prevention of recurrence.
Melanoma is a malignant neoplasm of the epidermal melanocytes. Awareness and early recognition of pigmented lesion inside oral cavity helps in initial diagnosis and further investigation and treatment. Oral malignant melanoma is a rare aggressive neoplasm commonly seen among middle age. The diagnosis of melanoma initiates from the pre-existing pigmented lesions. The poor prognosis of oral melanomas requires that pigmented lesions of undetermined origin be routinely biopsied. A case of malignant melanoma of hard palate with its clinical, radiological and histopathological presentation along with brief review is presented. Prognosis of these lesion is poor with survival rate of 5 years.
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