Binding Pattern Determination Of Class of Antifungal Drugs

Crystal Structure of cytochrome p450 2B4 has 476 amino acids, through docking approach we have attempted to explain the specificity of CYP2B4, total 28 imidazole drug were used for the studies as antifungal drugs in which bound bifonazole (reference) shows the binding energy of -8.67 kcal/mol .Compound Miconazole shows the minimum binding energy of -10.45 kcal/mol. The 2B4-bifonazole structure identified 10 residues (ALA 298, GLY 299, GLU 301, THR 302, ILE 363, VAL 292) within 6.5 Å of the active site of bifonazole. GLU 301, THR 302 are also located in 6.5 Å of the bound ligand in 2B4 structure. Due to the presence of the multiple binding substrates in cytochrome p450, it acts as the major target of many drugs in xenobiotic metabolism.
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An Overview on Fast Disintegrating Sublingual Tablets

The demand of fast disintegrating tablets has been growing during the last decade, due to the characteristics of fast disintegrating sublingual tablets for the potential emergency treatment. In terms of permeability, the sublingual area of the oral cavity (i.e, the floor of the mouth) is more permeable than the buccal (cheek) area, which in turn is more permeable than the palatal (roof) of the mouth. Drug delivery through the oral mucous membrane is considered to be a promising alternative to the oral route. Fast disintegrating sublingual tablets may lead to significant improvements over current treatment options for specific patient group, for instance pediatric and geriatric patients. This review highlights the mechanism of sublingual absorption, factors affecting sublingual absorption, formulation techniques, types of sublingual tablets, advantages, evaluation parameters and commercially available sublingual dosage forms

Molecular determinants and interaction data of cyclic peptide inhibitor with the extracellular domain of TrkB receptor

TrkB is a high affinity receptor for the brain derived neurotrophic factor (BDNF) and its phosphorylation stimulates activation of several intracellular signalling pathways linked to cellular growth, differentiation and maintenance. Identification of various activators and inhibitors of the TrkB receptor and greater understanding their binding mechanisms is critical to elucidate the biochemical and pharmacological pathways and analyse various protein crystallization studies. The data presented here is related to the research article entitled Brain Derived neurotrophic factor is involved in the regulation of glycogen synthase kinase 3β (GSK3β) signalling [1]. Cyclotraxin B (CTXB) is a disulphide bridge linked cyclic peptide molecule that interacts with TrkB receptor and inhibits the BDNF/TrkB downstream signalling. This article reports for the first time binding mechanism and interaction parameters of CTXB with the TrkB receptor. The molecular model of CTXB has been generated and it\u27s docking with TrkB domain carried out to determine the critical residues involved in the protein peptide interaction. © 2016 The Authors

Antimicrobial Activity Of New Synthetic Derivative Of Sesamol And Sesamum Indicum Seeds Extract Against Meningitis Causing Bacteria

The facts over S. aureus and E. coli to cause meningitis, and the antimicrobial potential of Sesame seeds and Sesamol were motivation for present study to compare the antibacterial potential of new synthetic derivativeof Sesamol (SDS) and Sesamum indicum seeds extract against meningitis causing bacteria (MCB). Present study involved synthesis of SDS and preparation of sesame seeds extract. The SDS was characterized using ATR-IR, 1H-NMR and Mass spectrometric data. Both SDS and sesame extract were tested for the inhibitory potential against MCB, namely: S. aureus and E. coli. Among both, the SDS exhibited higher inhibitory potential when compared with sesame extract. Based on the results present study concludes that SDS possess high inhibition potential against MCB and recommends that SDSmust be further evaluated for its clinical significance

Formulation and Evaluation of Cefotaxime Sodium Loaded Emulgel for Topical Bacterial Infections

The bacterial infections are very common and become a serious issue like in case of infections of one and more reproductive organ, inflammation on protective membrane of brain and spinal cord, inflammation of lungs air sacs, body drainage system infections, problem in body’s extreme response and infection caused by sexually transmitted bacteria in male and female. Generally, these bacterial infections are treated by using antibiotics like cefotaxime that is a semisynthetic, β-lactamase resistant, third-generation broad-spectrum cephalosporin. The common side effects of cefotaxime are uneasiness of stomach before vomiting, sneezing, itching. The topical antibacterial dosage forms like creams, gel, and ointment have some demerits and low duration of drug release. The emulgel is an alternative for topical drug delivery with several merits like enhanced skin penetration and improved bioavailability, reduced dosing, improved patient acceptability with targeted drug delivery, freedom of termination of the therapy at any time, drug delivery in controlled fashion for prolong duration. The aim of study was to develop a biphasic promising drug delivery system emulgel of cefotaxime. The 23 experimental design was used to prepare various emulgel batches to determinant the effect of liquid paraffin, span 20 and tween 20 on the performance of emulgel. The Batch F1 showed the maximum drug release while batch F8 up to 240 minutes. The drug release kinetics study of Batch F8 showed the Higuchi-Matrix as a best fit model and the Fickian Diffusion as a mechanism of drug release with R2 value 0.9158 and K value 8.4741

Amyloid β Induces Early Changes in the Ribosomal Machinery, Cytoskeletal Organization and Oxidative Phosphorylation in Retinal Photoreceptor Cells

Amyloid β (Aβ) accumulation and its aggregation is characteristic molecular feature of the development of Alzheimer’s disease (AD). More recently, Aβ has been suggested to be associated with retinal pathology associated with AD, glaucoma and drusen deposits in age related macular degeneration (AMD). In this study, we investigated the proteins and biochemical networks that are affected by Aβ in the 661 W photoreceptor cells in culture. Time and dose dependent effects of Aβ on the photoreceptor cells were determined utilizing tandem mass tag (TMT) labeling-based quantitative mass-spectrometric approach. Bioinformatic analysis of the data revealed concentration and time dependent effects of the Aβ peptide stimulation on various key biochemical pathways that might be involved in mediating the toxicity effects of the peptide. We identified increased Tau phosphorylation, GSK3β dysregulation and reduced cell viability in cells treated with Aβ in a dose and time dependent manner. This study has delineated for the first-time molecular networks in photoreceptor cells that are impacted early upon Aβ treatment and contrasted the findings with a longer-term treatment effect. Proteins associated with ribosomal machinery homeostasis, mitochondrial function and cytoskeletal organization were affected in the initial stages of Aβ exposure, which may provide key insights into AD effects on the photoreceptors and specific molecular changes induced by Aβ peptide

Global estimates on the number of people blind or visually impaired by cataract: a meta-analysis from 2000 to 2020

Background: To estimate global and regional trends from 2000 to 2020 of the number of persons visually impaired by cataract and their proportion of the total number of vision-impaired individuals. Methods: A systematic review and meta-analysis of published population studies and gray literature from 2000 to 2020 was carried out to estimate global and regional trends. We developed prevalence estimates based on modeled distance visual impairment and blindness due to cataract, producing location-, year-, age-, and sex-specific estimates of moderate to severe vision impairment (MSVI presenting visual acuity &lt;6/18, ≥3/60) and blindness (presenting visual acuity &lt;3/60). Estimates are age-standardized using the GBD standard population. Results: In 2020, among overall (all ages) 43.3 million blind and 295 million with MSVI, 17.0 million (39.6%) people were blind and 83.5 million (28.3%) had MSVI due to cataract blind 60% female, MSVI 59% female. From 1990 to 2020, the count of persons blind (MSVI) due to cataract increased by 29.7%(93.1%) whereas the age-standardized global prevalence of cataract-related blindness improved by −27.5% and MSVI increased by 7.2%. The contribution of cataract to the age-standardized prevalence of blindness exceeded the global figure only in South Asia (62.9%) and Southeast Asia and Oceania (47.9%). Conclusions: The number of people blind and with MSVI due to cataract has risen over the past 30 years, despite a decrease in the age-standardized prevalence of cataract. This indicates that cataract treatment programs have been beneficial, but population growth and aging have outpaced their impact. Growing numbers of cataract blind indicate that more, better-directed, resources are needed to increase global capacity for cataract surgery.</p

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Global estimates on the number of people blind or visually impaired by cataract : a meta-analysis from 2000 to 2020

DATA AVAILABILITY : Data sources for the Global Vision Database are listed at the following weblink http://www.anglia.ac.uk/verigbd. Fully disaggregated data is not available publicly due to data sharing agreements with some principal investigators yet requests for summary data can be made to the corresponding author.CHANGE HISTORY 16 July 2024 : A Correction to this paper has been published: https://doi.org/10.1038/s41433-024-03161-7.BACKGROUND : To estimate global and regional trends from 2000 to 2020 of the number of persons visually impaired by cataract and their proportion of the total number of vision-impaired individuals. METHODS : A systematic review and meta-analysis of published population studies and gray literature from 2000 to 2020 was carried out to estimate global and regional trends. We developed prevalence estimates based on modeled distance visual impairment and blindness due to cataract, producing location-, year-, age-, and sex-specific estimates of moderate to severe vision impairment (MSVI presenting visual acuity <6/18, ≥3/60) and blindness (presenting visual acuity <3/60). Estimates are age-standardized using the GBD standard population. RESULTS : In 2020, among overall (all ages) 43.3 million blind and 295 million with MSVI, 17.0 million (39.6%) people were blind and 83.5 million (28.3%) had MSVI due to cataract blind 60% female, MSVI 59% female. From 1990 to 2020, the count of persons blind (MSVI) due to cataract increased by 29.7%(93.1%) whereas the age-standardized global prevalence of cataract-related blindness improved by −27.5% and MSVI increased by 7.2%. The contribution of cataract to the age-standardized prevalence of blindness exceeded the global figure only in South Asia (62.9%) and Southeast Asia and Oceania (47.9%). CONCLUSIONS : The number of people blind and with MSVI due to cataract has risen over the past 30 years, despite a decrease in the age-standardized prevalence of cataract. This indicates that cataract treatment programs have been beneficial, but population growth and aging have outpaced their impact. Growing numbers of cataract blind indicate that more, better-directed, resources are needed to increase global capacity for cataract surgery.Brien Holden Vision Institute, Fondation Thea, Fred Hollows Foundation, Bill & Melinda Gates Foundation, Lions Clubs International Foundation (LCIF), Sightsavers International, and University of Heidelberg. Open Access funding enabled and organized by CAUL and its Member Institutions.https://www.nature.com/eyehj2024School of Health Systems and Public Health (SHSPH)SDG-03:Good heatlh and well-bein

Molecular mechanisms of neuronal death in glaucoma: development of a gene therapy approach for neuroprotection

Empirical thesis.Bibliography: pages 207-238.Chapter 1. Introduction -- Chapter 2. Material and methods -- Chapter 3. Protective role of brain derived neurotrophic factor in neuronal cells -- Chapter 4. mechanistic insights into the pharmacological targeting of TrkB receptor -- Chapter 5. Effect of TrkB modulation by PTPN11 gene targeting in SH-SY5Y cells -- Chapter 6. SHP2 upregulation impair inner retinal environment and negatively regulates TrkB receptor activity -- Chapter 7. SHP2 gene therapy is effective in RGC neuroprotection in experimental glaucoma -- Chapter 8. Conclusion and future directions -- References.In glaucoma, loss of retinal ganglion cells (RGCs) and axons leads to blindness; preservation of RGC neurons is therefore a major therapeutic goal. Increasing pressure (intraocular pressure, IOP) is a major risk factor in primary open angle glaucoma (POAG). Therapeutic lowering of IOP has been shown to be protective against glaucoma. However, despite IOP lowering many patients continue to demonstrate progressive glaucomatous neuropathy thus warranting additional intervention strategies. Brain-derived neurotrophic factor (BDNF) and its high affinity receptor tropomyosin receptor kinase B (TrkB) are reported to play important role in preservation of RGCs. In this thesis, I have investigated BDNF-TrkB signaling in neuronal cells and have explored the binding pattern of agonist and antagonist to the neurotrophin receptors. I have also investigated TrkB activity by modulating Shp2 phosphatase (PTPN11) in SH-SY5Y cells, in both healthy rodents and an experimental glaucoma animal model, using viral vector gene therapy. The results show that BDNF regulates the GSK3β activity in RGC-5, PC-12 and animal RGCs. Shp2 modulation regulates TrkB phosphorylation and endoplasmic stress response in SH-SY5Y and in the RGCs of both healthy and experimental glaucoma animal models. Shp2 overexpression in SH-SY5Y cells and animal retina, was associated with TrkB antagonism, reduced neuritogenesis, loss of retinal structural & functional integrity and enhanced ER stress response leading to apoptotic changes. Conversely, Shp2 knock down in an animal model of elevated IOP resulted in protection of the retinal structural and functional integrity. These observations correlated with enhanced TrkB phosphorylation in RGCs in response to genetic knockdown of Shp2 expression in experimental animal glaucoma model. The current findings reinforce the role played by Shp2 in regulating signaling in neuronal cells and highlight that Shp2 dysregulation is detrimental for the inner retina. Based on these observations we propose that selective targeting of Shp2 in RGCs may be a promising therapeutic strategy in glaucoma.Mode of access: World wide web1 online resource (xxi, 238 pages) colour illustration