2-[2-(4-(trifluoromethyl)phenylamino)thiazol-4-yl]acetic acid (Activator-3) is a potent activator of AMPK

AMPK is considered as a potential high value target for metabolic disorders. Here, we present the molecular modeling, in vitro and in vivo characterization of Activator-3, 2-[2-(4-(trifluoromethyl)phenylamino)thiazol-4-yl]acetic acid, an AMP mimetic and a potent pan-AMPK activator. Activator-3 and AMP likely share common activation mode for AMPK activation. Activator-3 enhanced AMPK phosphorylation by upstream kinase LKB1 and protected AMPK complex against dephosphorylation by PP2C. Molecular modeling analyses followed by in vitro mutant AMPK enzyme assays demonstrate that Activator-3 interacts with R70 and R152 of the CBS1 domain on AMPK γ subunit near AMP binding site. Activator-3 and C2, a recently described AMPK mimetic, bind differently in the γ subunit of AMPK. Activator-3 unlike C2 does not show cooperativity of AMPK activity in the presence of physiological concentration of ATP (2 mM). Activator-3 displays good pharmacokinetic profile in rat blood plasma with minimal brain penetration property. Oral treatment of High Sucrose Diet (HSD) fed diabetic rats with 10 mg/kg dose of Activator-3 once in a day for 30 days significantly enhanced glucose utilization, improved lipid profiles and reduced body weight, demonstrating that Activator-3 is a potent AMPK activator that can alleviate the negative metabolic impact of high sucrose diet in rat model

A Study on Oral Mucosal Lesions in 3500 Patients with Dermatological Diseases in South India

Background: Oral mucosal lesions that are observed in the dermatological diseases are categorized under mucocutaneous conditions. The oral lesions in dermatological diseases may be the early aspects of the disease manifestation or the most significant clinical appearance or the only sign/and or symptom of such dermatological diseases and occasionally lesions occur simultaneously in the skin as well as mucous membrane. Aim: This present study attempts to find out the prevalence of oral mucosal lesions in patients with dermatological diseases. Subjects and Methods: The study includes 3500 patients who attended out‑patient Department of Dermatology. Patients with oral manifestation were subjected for clinical examination in the Department of Oral Pathology. Diagnostic procedures were performed to confirm the clinical oral diagnosis. The results of the study were analyzed by SPSS software version 19.0 (Armonk, NY) and presented as descriptive statistics. Correlation of oral manifestions with their respective dermatological disease was statistically analysed by Pearson’s correlation test.(P < 0.05 were considered as statistically significant) Results: The prevalence rate of oral mucosal lesions in the present study was 1.8% (65/3500). The most frequent lesions observed were psoriasis 32.3% (21/65), lichen planus 18.4% (12/65), Stevens Johnson Syndrome 18.4% (12/65), pemphigus 10.7% (7/65), toxic epidermal necrolysis 4.6% (3/65), systemic lupus erythematosus 3% (2/65), discoid lupus  erythematosus 1.5% (1/65), pemphigoid 1.5% (1/65). Gender distribution in the study population was statistically significant (P < 0.001). Employed and unemployed individuals in the study population were statistically significant (P < 0.001). Pearson’s correlation analysis of oral manifestations with their respective dermatological disease showed r = 0.466 and signifies a positive correlation and is statistically significant at the 0.01 level (two‑tailed). Conclusion: The prevalence rate of oral mucosal lesions in patients with dermatological diseases was relatively low. However, predominant oral mucosal lesions observed in the study were autoimmune in origin with a high morbidity and mortality index. Hence, multidisciplinary approach will definitely help in the prognosis of patients.Keywords: Autoimmune disease, Dermatological manifestations, Immunofluorescence, India, Oral lesions, Prevalenc

Immunofluorescence and its application in dermatopathology with oral manifestations: Revisited

The use of fluorescence probes the field of cell and molecular biology. Immunofluorescence is a molecular method for detection of antigen or antibody in a tissue section/serum sample. Although histopathology remains gold standard for most of auto immune, immune mediated and vesiculo - bullous diseases. Immunofluorescence is an ancillary investigation, which are used to support clinical diagnosis more evidently. This method provides additional diagnostic, prognostic information and remains more specific diagnostic aid for vesiculo - bullous diseases of skin. This review article discusses about immunofluorescence techniques and its application in dermatopathology with oral manifestations

Molecular docking approach on the binding stability of derivatives of phenolic acids (DPAs) with Human Serum Albumin (HSA): Hydrogen-bonding versus hydrophobic interactions or combined influences?

Molecular docking (Mol.Doc) techniques were employed to ascertain the binding affinity and energetics of hydroxy derivatives of benzoic and cinnamic acids extract from Psidium guajava L. with Human Serum Albumin (HSA). Caffeic acid (CA), Ferullic acid (FA), Sinapic acid (SA), Syringic acid (SyA) and Vanillic acid (VA) are the derivatives phenolic acids (DPA) employed in docking studies which acts as the guest molecule. Docking of various feasible conformers of DPA with HSA (host) was explored and these conformers were categorized based on the docking score which is correlated to the binding energy (BE) and the stability depends upon the molecular interactions. Among the phenolic acids, SA-HSA complex was energetically more favorable and feasible based on BE and the order of binding stability upon complex formation of various DPA-HSA follows the order SA > FA = CA > VA > SyA, though SA and SyA are structurally similar to each other, likewise FA and VA exhibit a similar structure. The stability upon complex formation is correlated to the docking of the guest molecule in the binding domains of HSA and several molecular interactions. Hydrogen-bonding (HB) interaction governs the stability of host-guest complex is established. Interestingly, the presence of multiple hydrophobic interactions (pi-pi, pi-alkyl, pi-cation or anion, pi-sigma and pi-amide) competes over HB interaction in several conformers resulting in a decrease in BE. We report that SA acts as an excellent site selective and site-specific ligand that prefers to dock in Sudlow binding site II comprising of sub domains IIIA and IIIB respectively. However, all other phenolic acids do not behave neither as site selective nor site specific ligand such that they prefer to reside both in site II and site III (non-Sudlow binding site) of HSA. We authenticate that all the DPA as well as the amino acid moieties in HSA act as HB donor as well as acceptor sites apart from several hydrophobic interactions. We further establish that all the DPA has the least probable affinity to reside in binding site I (warfarin binding site), whereas sub domain IIIA of site II is the most preferred site which is energetically most favoured among all the sub domains