Search

Aims: Almost, one third of the world's urban population resides in slums and the number would double by 2030. Slums denotes collection of people from various communities having a meagre income and living in unhygienic conditions thus making themselves most vulnerable for outbreaks of communicable diseases. India contributes substantially to the global disease burden and under-five mortality rates i.e. 20% attributable to vaccine preventable diseases. Immunization plays a crucial role in combating high childhood mortality rates attributable to vaccine preventable diseases across the globe. This systematic review, provides insights on immunization status in slums, identifies various factors influencing it thus, exploring opportunities that may be available to improve vaccination coverage under the National Immunization Program.Methods: Taking into account the above aspects, a review of literature was undertaken in various databases that included studies published between 2006 and 2017.Results: In India, ~33% of the urban population lives in slums with suboptimal vaccination coverage ranging from 14% to upto 90%. Few of the important causes for low coverage included socioeconomic factors such as poor community participation, lack of awareness, frequent migration, and loss of daily income. Hence, mere presence of vaccines in the National Immunization Program doesn't do the job, there is a definite unmet need to emphasize upon the importance of immunization among slums dwellers and take necessary steps. For instance, delivering immunization services at the doorstep (e.g. pulse polio program), community-based education, text messaging as reminders and incentivized immunization services are some of the opportunities that can be explored and implemented to improve immunization status in the slums.Conclusion: Thus, in addition to inclusion of more and more vaccines in the National Immunization Program, there is a definite need to focus on people living in high risk areas in order to improve coverage and healthcare indicators. [ABSTRACT FROM AUTHOR]

Toxicological stress in aquatic organisms is caused by the discharge of hundreds of toxic pollutants and contaminants among which the current study concentrates on the toxic effect of non-steroidal anti-inflammatory drug ibuprofen (IBF) and the trace element selenium (Se). In this study, IBF and Se toxicity on freshwater mussel Lamellidens marginalis was studied for 14 days, and in silico predictions for their degradation were made using Molecular modelling and Quantum Mechanical approaches. The degrading propensity of cytochrome c oxidase proteins from Trametes verticillatus and Thauera selenatis (Turkey tail fungi and Gram-negative bacteria) is examined into atom level. The results of molecular modelling study indicate that ionic interactions occur in the T. selenatis -HEME bound complex by Se interacting directly with HEME, and in the T. versicolor -HEME bound complex by IBF bound to a nearby region of HEME. Experimental and theoretical findings suggest that, the toxicological effects of Se and IBF pollution can be reduced by bioremediation with special emphasis on T. versicolor , and T. selenatis , which can effectively interact with Se and IBF present in the environment and degrade them. Besides, this is the first time in freshwater mussel L. marginalis that ibuprofen and selenium toxicity have been studied utilizing both experimental and computational methodologies for their bioremediation study. [Display omitted] • Mussels increased their metabolism with increasing concentration gradient (IBF + Se). • Cellular damage and decreased redox balance in all exposure conditions. • Predictions for degradation by Molecular modelling and Quantum Mechanics. • Genotoxicity and histological damage were found regardless the treatment. [ABSTRACT FROM AUTHOR]

• AI methods Accelerated Drug Screening and Design with structure and Ligand-based methods. • AI Learning models for categorizing data-driven drug discovery. • Applications and Limitations of AI models for drug discovery in pharmaceutical industries. • Need for balance between AI-driven predictions and experimental validations. Artificial intelligence (AI), particularly deep learning as a subcategory of AI, provides opportunities to accelerate and improve the process of discovering and developing new drugs. The use of AI in drug discovery is still in its early stages, but it has the potential to revolutionize the way new drugs are discovered and developed. As AI technology continues to evolve, it is likely that AI will play an even greater role in the future of drug discovery. AI is used to identify new drug targets, design new molecules, and predict the efficacy and safety of potential drugs. The inclusion of AI in drug discovery can screen millions of compounds in a matter of hours, identifying potential drug candidates that would have taken years to find using traditional methods. AI is highly utilized in the pharmaceutical industry by optimizing processes, reducing waste, and ensuring quality control. This review covers much-needed topics, including the different types of machine-learning techniques, their applications in drug discovery, and the challenges and limitations of using machine learning in this field. The state-of-the-art of AI-assisted pharmaceutical discovery is described, covering applications in structure and ligand-based virtual screening, de novo drug creation, prediction of physicochemical and pharmacokinetic properties, drug repurposing, and related topics. Finally, many obstacles and limits of present approaches are outlined, with an eye on potential future avenues for AI-assisted drug discovery and design. [ABSTRACT FROM AUTHOR]

In this work, an analytical drain current model for Gate and Channel Engineered RingFET (GCE-RingFET) has been developed by solving 2D-Poisson equation in cylindrical coordinates. The authenticity of proposed model for GCE-RingFET architecture has been justified by comparing the analytical results with simulation results obtained using ATLAS 3D device simulation. Performance comparison of GCE-RingFET with the conventional RingFET device architectures has been performed. Various important performance metrics such as surface potential, transfer characteristic (I ds -V gs ), I ON /I OFF ratio, Threshold voltage roll off, Sub-threshold Slope (SS), Drain Induced Barrier Lowering (DIBL), Trans -conductance Generation Efficiency (g m /I ds ), have been investigated. [ABSTRACT FROM AUTHOR]

Some Turán type inequalities for Struve functions of the first kind are deduced by using various methods developed in the case of Bessel functions of the first and second kind. New formulas, like Mittag–Leffler expansion, infinite product representation for Struve functions of the first kind, are obtained, which may be of independent interest. Moreover, some complete monotonicity results and functional inequalities are deduced for Struve functions of the second kind. These results complement naturally the known results for a particular case of Lommel functions of the first kind, and for modified Struve functions of the first and second kind. [ABSTRACT FROM AUTHOR]

The genome of Leishmania donovani , the causative agent of visceral leishmaniasis, codes for approximately 65% of both conserved and non-conserved hypothetical proteins. Studies on ‘conserved hypothetical’ proteins are expected to reveal not only new and crucial aspects of Leishmania biochemistry, but it could also lead to discovery of novel drug candidates. Conserved hypothetical protein, LdBPK_070020, is a 31.14 kDa protein, encoded by an 810 bp gene. BLAST analysis of LdBPK_070020, performed against NCBI non-redundant database , showed 80–99% similarity with conserved hypothetical proteins of Leishmania belonging to other species. Using homologues recombination method, we have performed gene knockout of LdBPK_070020 and effects of the same were investigated on the parasite. The gene knocked out strain shows significant retardation in growth with respect to wild type. Detailed biochemical studies indicated towards important role of LdBPK_070020 in the parasite survival and growth. [ABSTRACT FROM AUTHOR]

Analyzing the health benefits of any two immunostimulants (synbiotics) in combined form and information on their interactions gain more visibility in the usage of synbiotics in aquafarms. With this intention, the current work explores the immunostimulant effect and structural interaction of synbiotic (β-1, 3 glucan binding protein from marine crab, Portunus pelagicus (Pp β-GBP) and Bacillus licheniformis) on Oreochromis mossambicus. The experimental diet was prepared with Pp β-GBP and B. licheniformis , and nourished to the fingerlings of O. mossambicus for 30 days. After the experimental trial, a higher growth rate and immune reactions (lysozyme, protease, myeloperoxidase and alkaline phosphatase activity) were noticed in the fish nourished with synbiotic (B. licheniformis and Pp β-GBP) enriched diet. Moreover, the synbiotic enriched diet elevated the antioxidant responses like glutathione peroxidase (GSH-Px) and catalase (CAT) activity in the experimental diet-nurtured fish. At the end of the feed trial, synbiotic diet nourished fish shows an increased survival rate during Aeromonas hydrophila infection, reflecting the disease resistance potential of experimental fish. Also, the interaction between Pp β-GBP and Bacillus licheniformis was analyzed through computational approaches. The results evidenced that, Pp β-GBP interacts with the B. licheniformis through sugar-based ligand, β-glucan through a hydrogen bond with a good docking score. Thus, the synbiotic diet would be an effective immunostimulant to strengthen the fish immune system for better productivity. • A synbiotic diet was prepared and nourished to the experimental fish Oreochromis mossambicus. • The growth rate was significantly increased in the fish fed with a synbiotic supplemented diet. • Immune responses and disease resistance were elevated in fish fed with a synbiotic enriched diet. • Molecular docking studies proved that β-glucan specifically binds to the active site of β-GBP. [ABSTRACT FROM AUTHOR]

Abstract: Molecular docking, free energy calculation and molecular dynamics (MD) simulation studies have been performed, to explore the putative binding modes of 3,5-diaminoindazoles, imidazo(1,2-b)pyridazines and triazolo(1,5-a) pyridazines series of Cyclin-dependent kinase (CDK2) inhibitors. To evaluate the effectiveness of docking protocol in flexible docking, we have selected crystallographic bound compound to validate our docking procedure as evident from root mean square deviations (RMSDs). We found different binding sites namely catalytic, inhibitory phosphorylation, cyclin binding and CKS-binding site of the CDK2 contributing towards the binding of these compounds. Moreover, correlation between free energy of binding and biological activity yielded a statistically significant correlation coefficient. Finally, three representative protein–ligand complexes were subjected to molecular dynamics simulation to determine the stability of the predicted conformations. The low value of the RMSDs between the initial complex structure and the energy minimized final average complex structure suggests that the derived docked complexes are close to equilibrium. We suggest that the phenylacetyl type of substituents and cyclohexyl moiety make the favorable interactions with a number of residues in the active site, and show better inhibitory activity to improve the pharmacokinetic profile of compounds against CDK2. The structure-based drug design strategy described in this study will be highly useful for the development of new inhibitors with high potency and selectivity. [Copyright &y& Elsevier]

Zika virus has been identified in various body fluids such as semen, urine, saliva, cerebrospinal fluid, and vaginal secretion of an infected individual. The pH of these fluids varies from mildly acidic to mildly alkaline. So it is imperative to understand the impact of these conditions on viral protein functioning. We investigated the NS2B-NS3 protease stability and its activity in different denaturing environments. Finding indicates that NS2B-NS3 protease maintains stability at pH 4.8–8.7. Thus it suggests that the complex remains functionally active to hydrolyze the polyprotein within a diverse environmental condition such as variable pH. Despite a stable structure at a broad pH range, a change in environmental conditions dramatically influence its protease activity. Moreover, it is susceptible to structural transformation leading to increased β-strand or helix content in the presence of alcohol. This study may help further to understand the folding-function relationship of the general flaviviral protease complex. Image 1 • Folding dynamics of NS2B-NS3 protease of Zika virus. • NS2B-NS3 protease has high structure stability at wide pH range and temperature. • HFIP and TFE induces helix rich secondary structure in NS2B-NS3 protease. • The NS2B-NS3 protease structure is susceptible to malleable folding. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Dihydroactinidiolide had powerful acetylcholinesterase inhibitory activity. • It had antioxidant and anti aggregation activity compared to the respective standards. • Dihydroactinidiolide was not cytotoxic towards N2A cells. • It increased viability of amyloid β treated N2A cells via reduced ROS generation. • Its ADME and hemolysis profiles were found to be safe. Abstract Synthesis of natural products has speeded up drug discovery process by minimizing the time for their purification from natural source. Several diseases like Alzheimer's disease (AD) demand exploring multi targeted drug candidates, and for the first time we report the multi AD target inhibitory potential of synthesized dihydroactinidiolide (DA). Though the activity of DA in several solvent extracts have been proved to possess free radical scavenging, anti bacterial and anti cancer activities, its neuroprotective efficacy has not been evidenced yet. Hence DA was successfully synthesized from β-ionone using facile two-step oxidation method. It showed potent acetylcholinesterase (AChE) inhibition with half maximal inhibitory concentration (IC 50) 34.03 nM, which was further supported by molecular docking results showing strong H bonding with some of the active site residues such as GLY117, GLY119 and SER200 of AChE. Further it displayed DPPH and (.NO) scavenging activity with IC 50 value 50 nM and metal chelating activity with IC 50 >270 nM. Besides, it significantly prevented amyloid β 25-35 self-aggregation and promoted its disaggregation at 270 nM. It did not show cytotoxic effect towards Neuro2a (N2a) cells up to 24 h at 50 and 270 nM while it significantly increased viability of amyloid β 25-35 treated N2a cells through ROS generation at both the concentrations. Cytotoxicity profile of DA against human PBMC was quite impressive. Hemolysis studies also revealed very low hemolysis i.e. minimum 2.35 to maximum 5.61%. It also had suitable ADME properties which proved its druglikeness. The current findings demand for further in vitro and in vivo studies to develop DA as a multi target lead against AD. [ABSTRACT FROM AUTHOR]

• α-bisabolol β-D-fucopyranoside (ABFP) was synthesized with 98% yield. • It exhibited Anti-cholinesterase, Antioxidant and Metal chelating activities. • It was found to have potent anti-aggregation and disaggregation properties. • It protected the Neuro 2a cells from Aβ 25-35 peptide induced neurotoxicity. • Overall, it can be suggested as a multi target drug against Alzheimer's disease. Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder affecting the elderly people. For the AD treatment, there is inefficiency in the existing medication, as these drugs reduce only the symptoms of the disease. Since multiple pathological proteins are involved in the development of AD, searching for a single molecule targeting multiple AD proteins will be a new strategy for the management of AD. In view of this, the present study was designed to synthesize and evaluate the multifunctional neuroprotective ability of the sesquiterpene glycoside α-bisabolol β-D-fucopyranoside (ABFP) against multiple targets like acetylcholinesterase, oxidative stress and β-amyloid peptide aggregation induced cytotoxicity. In silico computational docking and simulation studies of ABFP with acetylcholinesterase (AChE) showed that it can interact with Asp74 and Thr75 residues of the enzyme. The in vitro studies showed that the compound possess significant ability to inhibit the AChE enzyme apart from exhibiting antioxidant, anti-aggregation and disaggregation properties. In addition, molecular dynamics simulation studies proved that the interacting residue between Aβ peptide and ABFP was found to be involved in Leu34 and Ile31. Furthermore, the compound was able to protect the Neuro2 a cells against Aβ 25-35 peptide induced toxicity. Overall, the present study evidently proved ABFP as a neuroprotective agent, which might act as a multi-target compound for the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]