INSILICO DOCKING STUDIES TO IDENTIFY POTENT INHIBITORS OF ALPHA-SYNUCLEIN AGGREGATION IN PARKINSON DISEASE

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. Etiology of PD is progressive loss of dopaminergic neurons in Substantia nigra pars compacta (SNpc). One of the pathological hallmarks of PD is the presence of intracellular proteinaceous substances termed ‘Lewy bodies' composed of aggregated alpha-synuclein which is responsible for its toxic effect on SNpc. Hence any therapeutic target which blocks α-synuclein aggregation will provide a new channel to cure PD. Objective: The aim of the present study is to identify potent inhibitors (ligands) which binds to active site of α-synuclein and prevents self-association. Methods: In this study, insilico molecular docking was done against α-synuclein using five plant derived compounds namely (a) stimovul (b) 7,8dihydroxycoumarin, (c) etorphine (d) propoxyphene and (e) pentazdine. These compounds were analyzed for their Lipinski and ADMET properties using Accelrys Discovery studio 3.5. Molecular docking was performed between ligand and protein using Lead IT. Results: Results revealed that the best fit ligands against active site of α-synuclein were identified as Stimovul with a docking score of -4.5122 and the interacting amino acids were found to be SER 87 and VAL 95 followed by other compounds. Conclusion: These compounds which have the ability to bind to α-Synuclein insilico can be further developed using invitro and in vivo studies as a potent anti-parkinson drug.   Keywords: Parkinson disease, Substantia nigra, Molecular docking, Lipinski, ADMET

In vitro and in vivo evaluation of the biofilm-degrading Pseudomonas phage Motto, as a candidate for phage therapy

Infections caused by Pseudomonas aeruginosa are becoming increasingly difficult to treat due to the emergence of strains that have acquired multidrug resistance. Therefore, phage therapy has gained attention as an alternative to the treatment of pseudomonal infections. Phages are not only bactericidal but occasionally show activity against biofilm as well. In this study, we describe the Pseudomonas phage Motto, a T1-like phage that can clear P. aeruginosa infections in an animal model and also exhibits biofilm-degrading properties. The phage has a substantial anti-biofilm activity against strong biofilm-producing isolates (n = 10), with at least a twofold reduction within 24 h. To demonstrate the safety of using phage Motto, cytotoxicity studies were conducted with human cell lines (HEK 293 and RAW 264.7 macrophages). Using a previously established in vivo model, we demonstrated the efficacy of Motto in Caenorhabditis elegans, with a 90% survival rate when treated with the phage at a multiplicity of infection of 10

Ultrasound-guided compression method effectively counteracts Russell’s viper bite-induced pseudoaneurysm

Russell’s viper (Daboia russelii), one of the ‘Big Four’ venomous snakes in India is responsible for a majority of snakebite-induced deaths and permanent disabilities. Russell’s viper bites are known to induce bleeding/clotting abnormalities as well as myotoxic, nephrotoxic, cytotoxic and neurotoxic envenomation effects. In addition, they have been reported to induce rare envenomation effects such as priapism, sialolithiasis and splenic rupture. However, Russell’s viper bite-induced pseudoaneurysm (PA) has not been previously reported. PA or false aneurysm is a rare phenomenon that occurs in arteries following traumatic injuries includ-ing some animal bites, and it can become a life-threatening condition if not treated promptly. Here, we document two clinical cas-es of Russell’s viper bites where PA has developed despite antivenom treatment. Notably, a non-surgical procedure, ultra-sound-guided compression (USGC), either alone, or in combination with thrombin was effectively used in both the cases to treat the PA. Following this procedure and additional measures, the patients made complete recoveries without the recurrence of PA which were confirmed by subsequent examination and ultrasound scans. These data demonstrate the development of PA as a rare complication following Russell’s viper bites and the effective use of a simple, non-surgical procedure, USGC for the successful treatment of PA. These results will create awareness among healthcare professionals on the development of PA and the use of USGC in snakebite victims following Russell’s viper as well as other viper bites

Specific versus Non-Specific Immune Responses in an Invertebrate Species Evidenced by a Comparative de novo Sequencing Study

Our present understanding of the functioning and evolutionary history of invertebrate innate immunity derives mostly from studies on a few model species belonging to ecdysozoa. In particular, the characterization of signaling pathways dedicated to specific responses towards fungi and Gram-positive or Gram-negative bacteria in Drosophila melanogaster challenged our original view of a non-specific immunity in invertebrates. However, much remains to be elucidated from lophotrochozoan species. To investigate the global specificity of the immune response in the fresh-water snail Biomphalaria glabrata, we used massive Illumina sequencing of 5′-end cDNAs to compare expression profiles after challenge by Gram-positive or Gram-negative bacteria or after a yeast challenge. 5′-end cDNA sequencing of the libraries yielded over 12 millions high quality reads. To link these short reads to expressed genes, we prepared a reference transcriptomic database through automatic assembly and annotation of the 758,510 redundant sequences (ESTs, mRNAs) of B. glabrata available in public databases. Computational analysis of Illumina reads followed by multivariate analyses allowed identification of 1685 candidate transcripts differentially expressed after an immune challenge, with a two fold ratio between transcripts showing a challenge-specific expression versus a lower or non-specific differential expression. Differential expression has been validated using quantitative PCR for a subset of randomly selected candidates. Predicted functions of annotated candidates (approx. 700 unisequences) belonged to a large extend to similar functional categories or protein types. This work significantly expands upon previous gene discovery and expression studies on B. glabrata and suggests that responses to various pathogens may involve similar immune processes or signaling pathways but different genes belonging to multigenic families. These results raise the question of the importance of gene duplication and acquisition of paralog functional diversity in the evolution of specific invertebrate immune responses

Anticancer activity of Cynodon dactylon L. root extract against diethyl nitrosamine induced hepatic carcinoma

Background: Hepatocellular carcinoma is one of the most common cancers and a lethal disease. In view of the limited treatment and a grave prognosis of liver cancer, preventive control has been emphasized. Materials and Methods: The methanolic extract of roots of Cynodon dactylon was screened for its hepato-protective activity in diethyl nitrosamine (DEN) induced liver cancer in Swiss albino mice. The plant extract at a dose of 50 mg/kg was administered orally once a week, up to 30 days after DEN administration. The animals were sacrificed; blood sample and liver tissue were collected and used for enzyme assay such as, asparatate amino transferase (AST), alanine aminotransferase (ALT), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST). The liver marker enzymes AST and ALT produced signifi cant results in the protective action. Results: The antioxidant enzyme assay results concerning the improved activity of GPx, GST and CAT. These results concluded that enhanced levels of antioxidant enzyme and reduced amount of serum amino transaminase, which are suggested to be the major mechanisms of C. dactylon root extract in protecting the mice from hepatocarcinoma induced by DEN. These biochemical observations were supplemented by histopathological examination of liver sections. Conclusion: The methanolic extract of C. dactylon possesses signifi cant anticancer propertie