Ionic liquid tuned titanium dioxide nanostructures as an efficient colorimetric sensing platform for dopamine detection

Dopamine is a neurotransmitter distributed in the central and peripheral nervous system, its lower or higher production results in various pathological disorders. Various nanoparticles systems have been used in the sensing of dopamine while in the present work ionic liquid tuned titanium dioxide nanoparticles (TiO2 NPs) was first time evaluated in colorimetric detection of dopamine. TiO2 NPs have been synthesized by hydrothermal process and analyzed by different characterization techniques such as FTIR, XRD, and SEM that confirmed the desired synthesis. 1-H-3-methylimidazolium acetate (ionic liquid-a known conducting species) was prepared by the neutralization method. Colorimetric change in color from pinkish grey to reddish-brown with an increase in dopamine concentration was analyzed using a UV–Vis spectrophotometer. To optimize the protocol various parameters like nanoparticles loading, conc. of dopamine etc were optimized. The quantification and limit of detection for the proposed sensor were calculated as 2.55 × 10−7 M and 7.67 × 10−8 M respectively, and 1 × 10−8–3.6 × 10−6 M linear range with an R2 value of 0.9998. At an optimum temperature of 25 °C and at pH 12 the proposed sensor response time was just 4 min for dopamine detection. The proposed sensor has been also used for the dopamine detection in physiological solution. The proposed sensor showed good sensitivity and selectivity for dopamine sensing

Colorimetric based sensing of dopamine using ionic liquid functionalized drug mediated silver nanostructures

© 2020 Elsevier B.V. The present work reports the drug mediated synthesis of silver nanoparticles (AgNPs) for sensing of dopamine (biomarker Parkinson\u27s disease and others). Augmentin drug was chosen because of functionalities and aromaticity in its structure which will not only work in the synthesis of AgNPs but also enhance the electron density on nanoparticles (NPs) for better sensing properties. 1-H-3-methylimidazolium acetate ionic liquid (IL) having characteristic properties of aromaticity and conductivity were coated on to the surface of NPs to further enhance the mentioned properties. The FTIR, Raman spectroscopy and XRD analysis demonstrate the characteristic peaks assigned to AgNPs. SEM analysis shows round shaped morphology and EDX showed strong band for AgNPs. TGA analysis showed maximum degradation at 340 °C for the prepared AgNPs. The functionalized AgNPs/IL was used in sensing of dopamine. Different reaction conditions have been optimized to find the optimal performance of AgNPs/IL such as; (a) pH (b) amount of Ag/IL (c) time of incubation; (d) temperature. The response time of the proposed sensor for dopamine detection was only 4 min with a visible colorimetric change from light grey to brown color. The proposed sensor showed a wide linear range (1 × 10−8–3.6 × 10−6 M), low limit of detection 1.18 × 10−7 M, and limit of quantification 3.92 × 10−7 M with an R2 value of 0.9997. The IL capped Ag nano assembly exhibited no reactivity towards folic acid, urea, ascorbic acid, Ca+2, K+ and was successfully used to quantify dopamine in physiological sample

Fabrication of a colorimetric sensor using acetic acid-capped drug-mediated copper oxide nanoparticles for nitrite biosensing in processed food

Nitrite (NO2 −) and nitrate (NO3 −) are frequently used in cured meat products as preservatives, as they give a better taste and work well in color fixation. As a key possible carcinogen, excessive dietary consumption of NO2 − in cured meat products would be bad for health. Herein, copper oxide nanoparticles (CuO NPs) were synthesized using the drug Augmentin as a reducing and capping agent. The desired synthesis of CuO NPs was confirmed by various characterization techniques, including UV–visible spectroscopy, Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, thermal gravimetric analysis, X-ray diffraction, and scanning electron microscopy. The new approach of drug-mediated acetic acid-capped CuO NPs was developed for simple colorimetric detection of nitrite ions in a mimic solution of processed food. The color of the detection system changes from brown to yellow with the increase in the concentration of NO2 − and has been observed with the naked eye. The selectivity of the NO2 − detection system by the UV–visible spectrum and the naked eye is compared to other ions, such as Br−, I−, Cl−1, PO4 −3, CO3 2−, and SO4 2−. The platform was successfully employed for the determination of nitrite in real samples. Moreover, this probe can be used for the sensitive detection of NO2 − with a linear range of 1 × 10−8 to 2.40 × 10−6 M, a detection limit of 2.69 × 10−7 M, a limit of quantification 8.9 × 10−7 M, and a regression coefficient (R 2) of 0.997. Our results suggest that this sensor can be used for on-site analysis and quantification as well as in the fields of disease diagnosis, environmental monitoring, and food safety

Proteome level analysis of drug-resistant Prevotella melaninogenica for the identification of novel therapeutic candidates

The management of infectious diseases has become more critical due to the development of novel pathogenic strains with enhanced resistance. Prevotella melaninogenica, a gram-negative bacterium, was found to be involved in various infections of the respiratory tract, aerodigestive tract, and gastrointestinal tract. The need to explore novel drug and vaccine targets against this pathogen was triggered by the emergence of antimicrobial resistance against reported antibiotics to combat P. melaninogenica infections. The study involves core genes acquired from 14 complete P. melaninogenica strain genome sequences, where promiscuous drug and vaccine candidates were explored by state-of-the-art subtractive proteomics and reverse vaccinology approaches. A stringent bioinformatics analysis enlisted 18 targets as novel, essential, and non-homologous to humans and having druggability potential. Moreover, the extracellular and outer membrane proteins were subjected to antigenicity, allergenicity, and physicochemical analysis for the identification of the candidate proteins to design multi-epitope vaccines. Two candidate proteins (ADK95685.1 and ADK97014.1) were selected as the best target for the designing of a vaccine construct. Lead B- and T-cell overlapped epitopes were joined to generate potential chimeric vaccine constructs in combination with adjuvants and linkers. Finally, a prioritized vaccine construct was found to have stable interactions with the human immune cell receptors as confirmed by molecular docking and MD simulation studies. The vaccine construct was found to have cloning and expression ability in the bacterial cloning system. Immune simulation ensured the elicitation of significant immune responses against the designed vaccine. In conclusion, our study reported novel drug and vaccine targets and designed a multi-epitope vaccine against the P. melaninogenica infection. Further experimental validation will help open new avenues in the treatment of this multi-drug-resistant pathogen

Computer-aided identification of Mycobacterium tuberculosis resuscitation-promoting factor B (RpfB) inhibitors from Gymnema sylvestre natural products

Tuberculosis (TB), an infectious disease caused by multi-drug resistant Mycobacterium tuberculosis (Mtb), has been a global health concern. Mtb affects over a third of the world’s population, causing two million deaths annually due to its dormancy and propensity to spread infection during this period. Resuscitation-promoting factor B (RpfB) plays a pivotal role in the growth of Mtb during dormant periods, making it a critical target for eliminating Mtb and curing TB. Gymnema sylvestre is a famous medicinal plant with several medicinal properties, including antimicrobial activity; however, the therapeutic potential of the various reported metabolites of this plant against Mtb has not yet been explored. The aim of this study was to explore the reported natural products of G. sylvestre against the RpfB of the Mtb. A total of 131 reported secondary metabolites of this plant were collected and virtually screened against the RpfB. We particularly targeted the Glu292 residue of RpfB as it is crucial for the catalysis of this protein. From our in-house library, 114 compounds showed a binding affinity higher than the standard drug. The binding stability of the top three lead compounds was further confirmed through MD simulation analysis. Drug likeness analyses indicated that the ten hits had zero violations of the Lipinski rule of five. In addition, analyses of pharmacokinetics, toxicity, and target prediction revealed that the top compounds are devoid of toxicity and do not affect human proteins. Additionally, they reflect multifaceted approach as anti-TB agents. Our selected hits not only exhibit molecular properties favoring physiological compatibility but also exhibit properties enhancing their potential efficacy as therapeutic candidates. The compounds investigated here are worthy of experimental validation for the discovery of novel treatments against TB. Further, this study also provides a promising avenue for research on the pharmacological potential of G. sylvestre

Colorimetric sensing of uric acid based on sawdust-deposited silver nanoparticles via an eco-friendly and cost-effective approach

Uric acid is directly linked to gout, arthritis, neurological, cardiovascular, and kidney-related disorders. It is a byproduct obtained from the breakdown of purines and a significant indicator of hyperuricemia observed in both urine and blood. In the absence of any enzyme, it's quite difficult to develop a novel, cost-effective, and clinical method for uric acid detection. Herein, we report a very simple, low-cost, and non-enzymatic method for the selective identification and quantification of uric acid using green synthesized silver nanoparticles (Ag NPs). The desired Ag NPs were synthesized by the hydrothermal method using Erythrina suberosa sawdust as a deagglomeration agent and Psidium guajava extract as a reductant. The synthesis of the sensing platform, i.e., sawdust-deposited Ag NPs, was confirmed through different techniques such as UV-Vis spectrophotometer, FTIR, XRD, EDX, and scanning electron microscopy (SEM). Sawdust can offer a good, environmentally friendly, and cost-effective strategy to overcome the problem of agglomeration in nanoparticles. The enzyme mimic, with the help of H2O2, oxidizes the colorless 3,3′,5,5′-tetramethylbenzidine (TMB) to oxidized TMB with a blue-green color. The addition of uric acid reduces the oxidized TMB to a colorless product, resulting in a colorimetric change. For quality improvement, different reaction parameters, including pH, time, TMB, and NPs concentration, were optimized. Our proposed sensor responds in linear ranges of 0.04–0.360 μM, with a limit of quantification of 0.01 μM and a limit of detection of 0.004 μM. The suggested enzyme mimic detected uric acid in blood samples, with particular specificity in the presence of competitive analytes

mRNA Vaccine Designing Using Chikungunya Virus E Glycoprotein through Immunoinformatics-Guided Approaches

Chikungunya virus is an alphavirus transmitted by mosquitos that develops into chikungunya fever and joint pain in humans. This virus’ name originated from a Makonde term used to describe an illness that changes the joints and refers to the posture of afflicted patients who are affected by excruciating joint pain. There is currently no commercially available drug or vaccine for chikungunya virus infection and the treatment is performed by symptom reduction. Herein, we have developed a computationally constructed mRNA vaccine construct featuring envelope glycoprotein as the target molecule to aid in the treatment process. We have utilized the reverse vaccinology approach to determine epitopes that would generate adaptive immune reactions. The resulting T and B lymphocytes epitopes were screened by various immunoinformatic tools and a peptide vaccine construct was designed. It was validated by proceeding to docking and MD simulation studies. The following design was then back-translated in nucleotide sequence and codons were optimized according to the expression host system (H. sapiens). Various sequences, including 3′ and 5′ UTR regions, Kozak sequence, poly (A) tail, etc., were introduced into the sequence for the construction of the final mRNA vaccine construct. The secondary structure was generated for validation of the mRNA vaccine construct sequence. Additionally, in silico cloning was also performed to design a vector for proceeding towards in vitro experimentation. The proposed designed vaccine construct may proceed with experimental testing for further efficacy verification and the final development of a vaccine against chikungunya virus infection

Antidiabetic activities of alkaloids isolated from medicinal plants

Diabetes mellitus is a metabolic disorder affecting a great part of population around the world. It is the fifth leading death causing disease in the world and its cases are increasing day by day. Traditional medicine is thought to have promising future in the treatment of diabetes mellitus. In contrast to synthetic drugs phytochemicals are considered to be free from side effects. As one of the main class of natural products, alkaloids and their derivatives have been widely used as sources of pharmacological agents against a variety of medical problems. Many studies confirmed the role of alkaloids in the management of diabetes and numerous alkaloids isolated from different medicinal plants were found active against diabetes. Like other natural products, alkaloids regulate glucose metabolism either by inhibiting or inducing multiple candidate proteins including AMP-activated protein kinase, glucose transporters, glycogen synthase kinase-3, sterol regulatory element-binding proteins 1, glucokinase, glucose-6-phosphatase, acetyl-CoA carboxylase among the others. A comprehensive review of alkaloids reported in the literature with anti-diabetic activities and their target enzymes is conducted, with the aim to help in exploring the use of alkaloids as anti-diabetic agents. Future work should focus on rigorous clinical studies of the alkaloids, their development and relevant drug targets