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Objective Retinoschisis and Norrie disease are X-linked recessive retinal disorders caused by mutations in RS1 and NDP genes respectively. Both are likely to be monogenic and no locus heterogeneity has been reported. However, there are reports showing overlapping features of Norrie disease and retinoschisis in a NDP knock-out mouse model and also the involvement of both the genes in retinoschisis patients. Yet, the exact molecular relationships between the two disorders have still not been understood. The study investigated the association between retinoschisin (RS1) and norrin (NDP) using in vitro and in silico approaches. Specific protein–protein interaction between RS1 and NDP was analyzed in human retina by co-immunoprecipitation assay and MALDI-TOF mass spectrometry. STRING database was used to explore the functional relationship. Result Co-immunoprecipitation demonstrated lack of a direct interaction between RS1 and NDP and was further substantiated by mass spectrometry. However, STRING revealed a potential indirect functional association between the two proteins. Progressively, our analyses indicate that FZD4 protein interactome via PLIN2 as well as the MAP kinase signaling pathway to be a likely link bridging the functional relationship between retinoschisis and Norrie disease.

The conventional use of antibiotics for the treatment of infectious keratitis currently faces two major challenges: poor drug penetration and the emergence of antibiotic resistance in microbial strains. Cell-penetrating peptides (CPPs) with antimicrobial properties have the potential to address these challenges. However, their mode of action, mechanism of uptake, and interaction potential have not been explored in detail. In this study, we probed the mechanism of uptake and interaction potential of our previously designed peptides (VRF005 and VRF007). Our results showed that VRF005 undergoes direct translocation and induces a rough membrane surface, whereas VRF007 undergoes clathrin-mediated endocytic uptake. The gel shift assay showed that VRF005 is bound to genomic DNA, whereas VRF007 is bound to chitin and β-d-glucan. Gene expression studies revealed the effect of peptide VRF005 on Candida albicans transcription. Molecular docking and simulations showed that VRF005 forms noncovalent interactions (such as H-bonding and water bridges) with natamycin. It exhibited synergistic antifungal activity in the colony-forming assay. VRF005, functionalized in the polycaprolactone fiber matrix, showed sustained delivery and antifungal activity.

Herbs are widely utilized in the Western Ghats region of India to treat liver diseases and viral infections. However, such practices lack scientific evidence at the molecular level and may often pose adverse drug reactions. Thus, by this study we intend to identify phytocompounds having druggability and non-toxic profiles with potential activity against HBV-induced HCC. To startwith, the details of phytocompounds in traditionally utilized herbs in Western Ghats region were collated from chemical databases and publications. The druggability and toxicity of these compounds were predicted using MolSoft and ADVERpred, respectively. The probable targets of these phytocompounds were predicted using BindingDB. Moreover, compound-gene set pathways, cellular processes, and functional enrichment analysis were also performed using STRING and KEGG pathway databases. Subsequently, Herb-compound-target-disease pathway networks were constructed using Cytoscape 3.6.1. The potential hub protein was virtually screened against ligand dataset using POAP pipeline. Finally, molecular dynamics (MD) simulations of the most potential protein-ligand complexes were performed in triplicate using Desmond 6.1v. Amongst 274 compounds from 16 herbs studied, 36 showed drug likeness with nontoxic properties, and were also predicted to modulate 16 potential targets involved in the pathogenesis of HBV-induced HCC. Among all the molecules screened, flavonoids and diterpenoids from Andrographis paniculata and Thespesia populnea scored the highest edge count via modulating multiple targets and pathways. Moreover, molecular docking and MD simulation (100ns) also inferred that the top ranking Andrographin and Gossypetin to exhibit stable intermolecular interactions with EGFR protein, which was identified as highly connected hub protein in the constructed network. All these findings are suggestive of these moieties as potential therapeutics for targeting HBV-associated HCC sans adverse drug reactions.

CD147/Basigin/EMMPRIN (Extracellular Matrix Metalloproteinase inducer) is a single pass type1 transmembrane protein playing a central role in developmental process, wound healing, nutrient transport, inflammation, arthritis and also in microbial pathologies. It is also found to be a potent stimulator of MMP (matrix metalloproteinases) and has been considered as a prognostic marker in cancer. Dysregulation of CD147 is reported in several types of cancer. It activates cell proliferation, invasion, metastasis and inhibits tumor cell apoptosis under hypoxic condition. Thus, CD147 serves as a hub protein in cancer, as it is involved in several homophilic and heterophilic cellular interactions spanning the major hallmarks of cancer. Targeting these interactions is considered to be an efficient therapeutic modality in cancerous conditions. Hence, by this review we intend to collate the structure-function relationships of CD147, with an exclusive thrust on potential druggable hotspots based on its intra and inter molecular interactions.

We announce the coding-complete genome sequences of two isolates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from two coronavirus disease 2019 (COVID-19)-positive samples (RNA isolated from nasopharyngeal swabs) from Belagavi District, Karnataka State, India. Mutational analysis revealed the presence of the D614G substitution in both the isolates.

Mycotic keratitis is a fungal infection of corneal epithelium. It is more common in tropical and subtropical countries and is one of the leading causes of blindness. Many of the antifungal drugs have been less effective in treating this condition and certain drugs which are efficient and yet limited in use due to its extreme side effects. Hence, in this study an attempt is made to identify potential and least toxic antifungal inhibitors that targets thiamine thiazole synthase, a novel target for suppressing Fusarium solani subsp.pisi (Nectria haematococca MPVI) infections, to combat mycotic keratitis. Integrative computational approaches involving model refinement, molecular dynamics simulation and High throughput virtual screening (HTVS) were applied through integrative multi precision mode in order to identify potential inhibitors. Moreover, machine learning approach was also implemented to prioritize potential inhibitors that are ophthalmic adaptive, as well as antifungal molecule. From the NCI and Maybridge datasets, for HTVS only 209,872 compounds that surpassed ligand property filtration were considered, which resulted in 209 compounds after XP docking. Among the top 5 compounds from XP docking, on cumulative analysis only 2-(1-hydroxyethyl)-1,3-thiazole-4-carboxamide was prioritized as the most potential hit, as it showed higher order of significance in terms of binding affinity, structural stability and therapeutic relevance for the treatment of Mycotic keratitis. Thus, widening the scope for novel antifungal therapy in ophthalmic infections.

Aims Toxoplasma gondii (T. gondii) is an intracellular Apicomplexan parasite and a causative agent of toxoplasmosis in human. Its parasitic invasion leads to encephalitis, uveitis, chorioretinitis and congenital infection. Host invasion by T. gondii is mediated by Moving junction (MJ) complex formed by secretory proteins such as micronemes and Rhoptry Neck proteins (RONs). Among these secretory proteins, RON4 shows major interactions with RON2 and RON5 of MJ complex and is also found to facilitate invasion by interacting with β-tubulin of the host. Therefore, drug targeting of RON4 is considered to be an effective modality to inhibit host invasion. Main methods Hence, in this study, we have implemented High throughput virtual screening (HTVS) against predicted novel druggable cavity on RON4, in order to prioritize potential inhibitors. This study also specifically focuses on identifying potential drugs that are ocular accommodative towards targeting ocular toxoplasmosis. Thus, the small molecules resulting from HTVS were subjected to stringent multi-level precision screening which involves PASS prediction, Density functional theory analysis, Binding Free Energy Calculations and stability of complex formation during molecular dynamics simulation to prioritize the potential hits. Key findings Among the compounds from NCI chemical library, five (338683, 333739, 686585, 159706, 405935) were found to surpass all the stringent filtration criteria. Significance Based on comparatively analysis, it was inferred that 333739 (benzyl 2-((2-(((benzyloxy) carbonyl) amino)-3-hydroxybutanoyl) amino) propanoate) to be highly potential in comparison to other compounds and shall prove to be an efficient inhibitor of RON4 in ocular toxoplasmosis.

Methylene tetrahydrofolate reductase (MTHFR) is a flavoprotein, involved in one-carbon pathway and is responsible for folate and homocysteine metabolism. Regulation of MTHFR is pivotal for maintaining the cellular concentrations of methionine and SAM (S-adenosyl methionine) which are essential for the synthesis of nucleotides and amino acids, respectively. Therefore, mutations in MTHFR leads to its dysfunction resulting in conditions like homocystinuria, cardiovascular diseases, and neural tube defects in infants. Among these conditions, homocystinuria has been highly explored, as it manifests ocular disorders, cognitive disorders and skeletal abnormalities. Hence, in this study, we intend to explore the mutational landscape of human MTHFR isoform-1 (h.MTHFR-1) to decipher the most pathogenic variants pertaining to homocystinuria. Thus, a multilevel stringent prioritization of non-synonymous mutations in h.MTHFR-1 by integrative machine learning approaches was implemented to delineate highly deleterious variants based on its pathogenicity, impact on structural stability and functionality. Subsequently, extended molecular dynamics simulations and molecular docking studies were also integrated in order to prioritize the mutations that perturbs structural stability and functionality of h.MTHFR-1. In addition, displacement of Loop (Arg157-Tyr174) and helix α9 (His263-Ser272) involved in open/closed conformation of substrate binding domain were also probed to confirm the functional loss. On juxtaposed analysis, it was inferred that among 126 missense mutations screened, along with known pathogenic mutations (H127 T, A222 V, T227 M, F257 V and G387D) predicted that W500C, P254S and D585 N variants could be potentially driving homocystinuria. Thus, uncovering the prospects for inclusion of these mutations in diagnostic panels based on further experimental validations.

Glaucoma is the second leading cause of blindness in the world and is characterized by the loss of retinal ganglion cells (RGC) over a period of time, leading to complete blindness. Recently, endothelin has been identified as an important factor that influences intraocular pressure IOP, OBF, and direct RGC damage. Targeting the endothelin receptor signaling pathway in glaucoma is considered to be highly beneficial, as it can effectively modulate IOP, OBF, and RGC damage, the key factors which are essential to modulate the disease progression holistically. Currently, synthetic drugs like Bosentan, BQ-123, and prostaglandin analogues are available as endothelin receptor antagonists, which are extensively used in the treatment of cardiovascular and other conditions like systemic hypertension. However, the usage of these drugs in glaucoma is limited due to toxicity and poor bioavailability in the ocular milieu. Thus, there is a need for potential natural compounds as endothelin receptor antagonists that acts as dual inhibitors by targeting both ETA and ETB and are highly efficient with the least toxicity. Hence, this study is intended to prioritize endothelin receptor antagonists by structural bioinformatics approaches involving molecular modeling, molecular dynamics, and molecular docking studies. Subsequently, High throughput virtual screening (HTVS) vs. Natural compound databases targeting the optimal binding sites of both ETA and ETB. Following this, the common hits were subjected to binding free energy calculations (MMGBSA) and ADMETox analysis. Finally, the most potential hits were analyzed for MD based binding stability analysis and binding free energy. Similarly, the known synthetic inhibitors were also docked to the receptors and the results were analyzed. From this study, it was inferred that among the natural compounds dataset (8929 compounds), only 4 common compounds were identified as hits. Among these, only one compound ST075640 surpassed all the prioritization criteria including MMGBSA, ADMETox prediction, dual inhibitory potential (ETA & ETB), and also in structural comparative analysis with bosentan it showed similar efficiency. Thus, the validated hit shall prove to be effective in modulating endothelin mediated IOP, OBF, and RGC damage in glaucomatous condition.

Polycystic ovary syndrome (PCOS) is a complex disorder affecting approximately 5-10 percent of all women of reproductive age. It is a multi-factorial endocrine disorder, which demonstrates menstrual disturbance, infertility, anovulation, hirsutism, hyper androgenism and others. It has been indicated that differential expression of genes, genetic level variations, and other molecular alterations interplay in PCOS and are the target sites for clinical applications. Therefore, integrating the PCOS-associated genes along with its alteration and underpinning the underlying mechanism might definitely provide valuable information to understand the disease mechanism. We manually curated the information from 234 published literatures, including gene, molecular alteration, details of association, significance of association, ethnicity, age, drug, and other annotated summaries. PCOSDB is an online resource that brings comprehensive information about the disease, and the implication of various genes and its mechanism. We present the curated information from peer reviewed literatures, and organized the information at various levels including differentially expressed genes in PCOS, genetic variations such as polymorphisms, mutations causing PCOS across various ethnicities. We have covered both significant and non-significant associations along with conflicting studies. PCOSDB v1.0 contains 208 gene reports, 427 molecular alterations, and 46 phenotypes associated with PCOS.

Chlamydia trachomatis (C.t) is a gram-negative obligate intracellular bacteria, which is a major causative of infectious blindness and sexually transmitted diseases. A surge in multidrug resistance among chlamydial species has posed a challenge to adopt alternative drug targeting strategies. Recently, in C.t, L,L-diaminopimelate aminotransferase (CtDAP-AT) is proven to be a potential drug target due its essential role in cell survival and host nonspecificity. Hence, in this study, a multilevel precision-based virtual screening of CtDAP-AT was performed to identify potential inhibitors, wherein, an integrative stringent scoring and filtration were performed by coupling, glide docking score, binding free energy, ADMET (absorption, distribution, metabolism, and excretion, toxicity) prediction, density functional theory (quantum mechanics), and molecular dynamics simulation (molecular mechanics). On cumulative analysis, NSC_5485 (1,3-bis((7-chloro-4-quinolinyl)amino)-2-propanol) was found to be the most potential lead, as it showed higher order significance in terms of binding affinity, bonded interactions, favorable ADMET, chemical reactivity, and greater stabilization during complex formation. This is the first report on prioritization of small molecules from National Cancer Institute (NCI) and Maybridge data sets (341 519 compounds) towards targeting CtDAP-AT. Thus, the proposed compound shall aid in effective combating of a broad spectrum of C.t infections as it surpassed all the levels of prioritization.

X-linked retinoschisis (XLRS) is a retinal degenerative disorder caused by mutations in RS1 gene leading to splitting of retinal layers (schisis) which impairs visual signal processing. Retinoschisin (RS1) is an adhesive protein which is secreted predominantly by the photoreceptors and bipolar cells as a double-octameric complex. In general, XLRS patients show wide clinical heterogeneity, presenting practical challenges in disease management. Though researchers have attempted various approaches to offer an explanation for clinical heterogeneity, the molecular basis has not been understood yet. Therefore, this study aims at establishing a link between the phenotype and genotype based on the molecular mechanism exerted by the mutations. Twenty seven XLRS patients were enrolled, of which seven harboured novel mutations. The mutant constructs were genetically engineered and their secretion profiles were studied by in vitro cell culture experiments. Based on the secretory profile, the patients were categorized as either secreted or non-secreted group. Various clinical parameters such as visual acuity, location of schisis, foveal thickness and ERG parameters were compared between the two groups and control. Although the two groups showed severe disease phenotype in comparison with control, there was no significant difference between the two XLRS groups. However, the secreted group exhibited relatively severe disease indications. On the other hand molecular analysis suggests that most of the RS1 mutations result in intracellular retention of retinoschisin. Hence, clinical parameters of patients with non-secreted profile were analyzed which in turn revealed wide variability even within the group. Altogether, our results indicate that disease severity is not merely dependent on secretory profile of the mutations. Thus, we hypothesize that intricate molecular detail such as the precise localization of mutant protein in the cell as well as its ability to assemble into a functionally active oligomer might largely influence disease severity among XLRS patients.

Mycotic keratitis has emerged as a major ophthalmic problem and a leading cause of blindness, since its recognition in 1879. Filamentous fungi are major causative of mycotic keratitis. In India, the main etiological organism responsible for mycotic keratitis is Aspergillus species followed by Fusarium species. In South India, Fusarium based keratitis scales up to 43%. Nearly one-third of mycotic keratitis treatment results in failure, as fungal infections are highly resistant to antibiotic therapies. Therefore, there is need to determine novel and specific targets to constrain Fusarium infections in human eye. In this study, we implemented subtractive proteomics coupled with in silico functional annotation to prioritize potential and specific drug targets which can be used to modulate the virulence of Fusarium solani subsp.pisi (Nectria haematococca MPVI). The results infer that Thiamine thiazole synthase (Thi4), an intracellular membrane bound protein as the potential target, which is a core protein in biological and metabolic process of this pathogen. Moreover, this protein occurs in the thiamine thiazole biosynthesis pathway which is unique to F.solani and devoid in human. Hence, we predicted a plausible structure for this protein and also performed ligand-binding cavity analysis which can be for a strong base for drug designing studies. This study will pave way in better understanding of potential drug targets in F.solani and also leading to therapeutic interventions of fungal keratitis.

Background PPARγ is an isoform of peroxisome proliferator-activated receptor (PPAR) belonging to a super family of nuclear receptors. PPARγ receptor is found to play a crucial role in the modulation of lipid and glucose homeostasis. Its commotion has been reported to play a significant role in a broad spectrum of diseases such as type 2 diabetes mellitus, inflammatory diseases, Alzheimer’s disease, and in some cancers. Hence, PPARγ is an important therapeutic target. Polyunsaturated fatty acids (PUFAs) and their metabolites (henceforth referred to as bioactive lipids) are known to function as agonists of PPARγ. However, agonistic binding modes and affinity of these ligands to PPARγ are yet to be deciphered. Methods In this study, we performed a comparative molecular docking, binding free energy calculation and molecular dynamics simulation to infer and rank bioactive lipids based on the binding affinities with the ligand binding domain (LBD) of PPARγ. Results The results inferred affinity in the order of resolvin E1 > neuroprotectin D1 > hydroxy-linoleic acid > docosahexaenoic acid > lipoxin A4 > gamma-linolenic acid, arachidonic acid > alpha-linolenic acid > eicosapentaenoic acid > linoleic acid. Of all the bioactive lipids studied, resolvin E1, neuroprotectin D1 and hydroxy-linoleic acid showed significant affinity comparable to proven PPARγ agonist namely, rosiglitazone, in terms of Glide XP docking score, H-bond formation with the key residues, binding free energy and stable complex formation with LBD favouring co-activator binding, as inferred through Molecular Dynamics trajectory analysis. Conclusion Hence, these three bioactive lipids (resolvin E1, neuroprotectin D1 and hydroxy-linoleic acid) may be favourably considered as ideal drug candidates in therapeutic modulation of clinical conditions such as type 2 DM, Alzheimer’s disease and other instances where PPARγ is a key player.

Retinoblastoma (RB) is a malignant tumor of the retina seen in children, and potential non invasive biomarkers are in need for rapid diagnosis and for prognosticating the therapy. This study was undertaken to identify the differentially expressed miRNAs in the serum of children with RB in comparison with the normal age matched serum, to analyze its concurrence with the existing RB tumor miRNA profile, to identify its novel gene targets specific to RB, and to study the expression of a few of the identified oncogenic miRNAs in the advanced stage primary RB patient's serum sample. MiRNA profiling was performed on 14 pooled serum from children with advanced RB and 14 normal age matched serum samples, wherein 21 miRNAs were found to be upregulated (fold change ≥ +2.0, P ≤ 0.05) and 24 to be downregulated (fold change ≤ –2.0, P ≤ 0.05). Furthermore, intersection of 59 significantly deregulated miRNAs identified from RB tumor profiles with that of miRNAs detected in serum profile revealed that 33 miRNAs had followed a similar deregulation pattern in RB serum. Later we validated a few of the miRNAs (miRNA 17-92) identified by microarray in the RB patient serum samples (n = 20) by using qRT-PCR. Expression of the oncogenic miRNAs, miR-17, miR-18a, and miR-20a by qRT-PCR was significant in the serum samples exploring the potential of serum miRNAs identification as noninvasive diagnosis. Moreover, from miRNA gene target prediction, key regulatory genes of cell proliferation, apoptosis, and positive and negative regulatory networks involved in RB progression were identified in the gene expression profile of RB tumors. Therefore, these identified miRNAs and their corresponding target genes could give insights on potential biomarkers and key events involved in the RB pathway.

Multi Drug Resistance (MDR) is one of the major causes of chemotherapy failure in human malignancies. Curcumin, the active constituent of Curcuma longa is a proven anticancer agent potentially modulating the expression and function of these MDR proteins. In this study, we attempted to test curcumin for its potential to inhibit the expression and function of multidrug resistance associated protein 1 (MRP1) in retinoblastoma (RB) cell lines through western blot, RT-PCR and functional assays. In silico analysis were also performed to understand the molecular interactions conferred by curucmin on MRP1 in RB cells. Western blot and RTPCR analysis did not show any correlation of MRP1 expression with increase in concentration of curcumin. However, inhibitory effect of curcumin on MRP1 function was observed as a decrease in the efflux of fluorescent substrate. Moreover, Curcumin did not affect 8-azido-ATP-biotin binding to MRP1 and it also showed inhibition of ATP-hydrolysis stimulated by quercetin, which is indicative of curcumin's interaction with the substrate binding site of MRP1. Furthermore, homology modelling and docking simulation studies of MRP1 also provided deeper insights into the molecular interactions, thereby inferring the potential binding mode of curcumin into the substrate binding site of MRP1.

Peptidomimetics is a novel drug designing strategy in which an Insilico inhibitor is designed by mimicking the framework of a short peptide. Novel drug design str ate- gies shall only pave way for developing unique and safer anti-HIV drugs. In the present study, we propose a Peptidomimetics based gp120 attachment inhibitor. I n human biological system, HIV-1 interacts with CD4 r e- ceptor of the host via its surface glycoprotein gp1 20 es- tablishing initial attachment. This protein–protein inter- action interface forms the base to derive an inhibi tor mim- icking backbone of the receptor. The mimicked inhib itor derived in this study is based on the insilico interactions of soluble CD4 (SCD4) (precursor of CD4) with gp120 . The molecular interactions of SCD4 with gp120 were iden- tified by MEDock software. Furthermore, the interac ting interface was analyzed manually for topology, and t he backbone of the ligand molecule was sketched based on it with chemsketch. Moreover, the sketched ligand was op- timized and was docked with gp120 using Argus lab. Dock- ing results show six hydrogen bonds formation betwe en the ligand and binding interface of gp120. The liga nd was also found to be fit with good druggable character, as per Lipinski’s rule of five. Hence, this work addresses the drug likeness of the peptidomimetic ligand proposed.

Neocarzinostatin (NCS) a potent DNA-damaging, anti-tumor toxin extracted from Streptomyces carzinostaticus that recognizes double-stranded DNA bulge and induces DNA damage. 2 Fluoro (2F) Modified EpCAM RNA aptamer is a 23-mer that targets EpCAM protein, expressed on the surface of epithelial tumor cells. Understanding the interaction between NCS and the ligand is important for carrying out the targeted tumor therapy. In this study, we have investigated the biophysical interactions between NCS and 2-fluro Modified EpCAM RNA aptamer using Circular Dichroism (CD) and Infra-Red (IR) spectroscopy. The aromatic amino acid residues spanning the β sheets of NCS are found to participate in intermolecular interactions with 2 F Modified EpCAM RNA aptamer. In-silico modeling and simulation studies corroborate with CD spectra data. Furthermore, it reinforces the involvement of C and D1 strand of NCS in intermolecular interactions with EpCAM RNA aptamer. This the first report on interactions involved in the stabilization of NCS-EpCAM aptamer complex and will aid in the development of therapeutic modalities towards targeted cancer therapy.

We announce the draft genome sequence of two extensively drug-resistant Mycobacterium tuberculosis strains, VRFCWCF XDRTB 232 and VRFCWCF XDRTB 1028, isolated from the sputum samples of a patient clinically suspected to have tuberculosis, and we also report novel mutations that confer drug resistance.

We announce the draft genome sequence of a streptomycin monoresistant Mycobacterium tuberculosis strain (VRFCWCF MRTB 180) isolated from sputum of a clinically suspected tuberculosis patient.

Objective: To determine the possible interaction of curcumin with P-glycoprotein (P-gp) expression and function by in vitro and in silico studies. Materials and Methods: In this study, curcumin was compared for its potential to modulate the expression and function of P-gp in Y79 RB cells by western blot, RT-PCR (reverse transcription polymerase chain reaction) and functional assay. Further, in silico molecular modeling and docking simulations were performed to deduce the inhibitory binding mode of curcumin. Results: Western blot and RT-PCR analysis decreased the expression of P-gp in a dose-dependent manner. The effect of curcumin on P-gp function was demonstrated by Rhodamine 123 (Rh123) accumulation and efflux study. Curcumin increased the accumulation of Rh123 and decreased its efflux in retinoblastoma (RB) cells. In addition, curcumin inhibited verapamil stimulated ATPase activity and photoaffinity labeling study showed no effect on the binding of 8-azido-ATP-biotin, indicating its interaction at the substrate binding site. Moreover, molecular docking studies concurrently infer the binding of curcumin into the substrate binding site of P-gp with a binding energy of -7.66 kcal/mol. Conclusion: These findings indicate that curcumin suppresses the MDR1 expression and function, and therefore may be useful as modulators of multidrug resistance in RB tumor.

Background Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that is implicated in the regulation of food intake and body weight. Polyunsaturated fatty acids (PUFAs) localised in cell membranes have been shown to alter the levels of BDNF in the brain, suggesting that PUFAs and BDNF could have physical interaction with each other. To decipher the molecular mechanism through which PUFAs modulates BDNF’s activity, molecular docking was performed for BDNF with PUFAs and its metabolites, with 4-Methyl Catechol as a control. Results Inferring from molecular docking studies, lipoxin A4 (LXA4), and a known anti-inflammatory bioactive metabolite derived from PUFAs, with a binding energy of −3.98 Kcal/mol and dissociation constant of 1.2mM showed highest binding affinity for BDNF in comparison to other PUFAs and metabolites considered in the study. Further, the residues Lys 18, Thr 20, Ala 21, Val 22, Phe 46, Glu 48, Lys 50, Lys 58, Thr 75, Gln 77, Arg 97 and Ile 98 form hot point motif, which on interaction enhances BDNF’s function. Conclusion These results suggest that PUFAs and their metabolites especially, LXA4, modulate insulin resistance by establishing a physical interaction with BDNF. Similar interaction(s) was noted between BDNF and resolvins and protectins but were of lesser intensity compared to LXA4.

Background HSV-1 genome is a mosaic of recombinants. Clinical Herpes simplex virus -1 (HSV1) isolates were already genotyped as A, B and C types based on nucleotide variations at Unique Short (US) 4 (gG) and US 7 (gI) regions through phylogeny. Analysis of Glycoprotein C (gC) exon present on the Unique Long (UL) region had also revealed the existence of different genotypes. Glycoprotein C is mainly involved in initial viral attachment to heparan sulphate on host cell surface facilitating the virus's binding and penetration into cell. As the amount of heparan sulphate on the host cell surface varies according to the cell type, it is plausible that different genotypes bind differentially to cell types. Hence, this study was framed to determine the existence of novel genotypes/sub genotypes in the US or UL regions which could associate with clinical entities. Results All the twenty five isolates analyzed in this study were of genotype A as per their gG gene sequences. In case of gI gene, 16 out of 25 were found to be type A and the remaining nine were type B putative intergenic recombinants. Intragenic recombinations were also encountered in both the US genes, with gG possessing novel subgenotypes, arbitrarily designated A1 and A2. The 9 type B isolates of gI genes also branched out into 2 clades due to genetic variations. Glycoprotein C of UL region had two distinct genotypic clades α and β, whose topological distribution was significantly different from that of the US region. Neither the US nor UL regions, however, showed any preference among the genotypes to a specific anatomic site of infection. Even the non synonymous variations identified in the functional domain of gC, were not confined to a particular genotype/clinical entity. Conclusion The analyses of the US and UL regions of the HSV-1 genome showed the existence of variegated genotypes in these two regions. In contrary to the documented literature, in which Asian strains were concluded as more conserved than European ones, our study showed the existence of a higher degree of variability among Indian strains. However, the identified novel genotypes and subgenotypes were not found associated with clinical entities.

Indian Plant Anticancer Compounds Database (InPACdb) is a web-based open access database of phytochemicals. The objective of this initiative is to project the potential of anticancer phytochemicals from Indian pharmacopoeia in an integrated environment. This database is unique in providing comprehensive information covering cancer type, molecular target, 3D Stereochemical structures (tautomers, stereoisomers, conformers and resonance structures) and Chemical descriptors etc. for each entry, enabling effective cheminformatics analysis. The complete dataset of InPACdb encompasses 32 descriptive fields for each entry, and is freely available for download at http://www.inpacdb.org.