Effect of hydroxybenzoic acids antioxidants on the oxidative stability of sardine oil

The antioxidant capacities of three derivatives of hydroxybenzoic acids (Gentisic acid, protochatechuic acid and vanillic acid) in sardine oil were compared. Peroxide value, conjugated diene value, p-anisidine value and thiobarbituric acid reactive substances (TBARS) value were assessed to determine the oxidative stability provided by these substances to the sardine oil. Results showed that gentisic acid (2,5 dihydroxy benzoic acid) was the most effective of the chosen hydroxybenzoic acids in imparting oxidative stability to the sardine oil. Protochatechuic acid (3,4 dihydroxy benzoic acid) provided relatively less oxidative stability, while vanillic acid had no effect. Results from this work showed that the position of hydroxylation and methyl substitution influences the antioxidant capacity of the molecules in sardine oil. Furthermore, it was found that the extent of oxidative stability conferred by the antioxidants in lipid systems is influenced by several other physical and chemical factors as well

Screening of polymeric membranes for membrane assisted deacidification of sardine oil

The diversification in fish oil use and the need for softer processing demand new oil refining processes. In considering the advantages of membrane technology, three different membranes (polyamide (PA), polytetrafluoroethylene (PTFE) and polyethersulfone (PES)) were used in this particular study. Preliminary results in the separation of free fatty acids (FFA) from glycerides of sardine oil/ethanol mixtures using a single dead end microfiltration mode have been reported here. The influence of experimental factors like pressure and oil/ethanol ratios (w/v) on the permeate flux and the reduction of FFA (%) in the permeate was studied. PTFE membrane showed promising results in terms of residual FFA in permeate (%), % oil loss (15.12%, 5.45%) as compared to PA (20.50%, 6.66%) and PES membranes (20.60%, 8.92%). PA membrane showed a higher flux of 4.4 L/m2 /h, followed by PTFE 3.34 L/m2 /h and PES, 1.19 L/m2 /h at 3.5 bar trans-membrane pressure. These results showed that using PTFE membrane could be an ideal strategy for the membrane assisted deacidification of sardine oil using solvents

Re-Routing Drugs to Blood Brain Barrier: A Comprehensive Analysis of Machine Learning Approaches With Fingerprint Amalgamation and Data Balancing

Computational drug repurposing is an efficient method to utilize existing knowledge for understanding and predicting their effect on neurological diseases. The ability of a molecule to cross the blood-brain barrier is a primary criteria for effective therapy. Thus, accurate predictions by employing Machine learning models can effectively identify the drug candidates that could be repurposed for neurological conditions. This study comprehensively analyzes the performance of the well-known machine learning models on two different datasets to overcome dataset-related biases. We found that random forest and extratrees (i.e., tree-based ensembled models) have the highest accuracy with mol2vec fingerprint for BBB permeability prediction, attaining AUC_ROC of 0.9453 and 0.9601 on BBB and B3DB dataset, respectively. Additionally, we have analyzed the impact of the data balancing technique (i.e., SMOTE) to improve the specificity of the models. Finally, we have explored the impact of different fingerprint combinations on accuracy. By employing SMOTE and fingerprint combination, SVC attains the highest AUC_ROC of 0.9511 on BBB dataset. Finally, we used the best-performing models of the B3DB dataset to evaluate the BBB permeability for drugs intended to be used for repurposing. Model validation for repurposing predicted the non-passage for most antihypertensive drugs and passage for CYP17A1 cancer drugs

In Silico Modeling as a Perspective in Developing Potential Vaccine Candidates and Therapeutics for COVID-19

The potential of computational models to identify new therapeutics and repurpose existing drugs has gained significance in recent times. The current ‘COVID-19’ pandemic caused by the new SARS CoV2 virus has affected over 200 million people and caused over 4 million deaths. The enormity and the consequences of this viral infection have fueled the research community to identify drugs or vaccines through a relatively expeditious process. The availability of high-throughput datasets has cultivated new strategies for drug development and can provide the foundation towards effective therapy options. Molecular modeling methods using structure-based or computer-aided virtual screening can potentially be employed as research guides to identify novel antiviral agents. This review focuses on in-silico modeling of the potential therapeutic candidates against SARS CoVs, in addition to strategies for vaccine design. Here, we particularly focus on the recently published SARS CoV main protease (Mpro) active site, the RNA-dependent RNA polymerase (RdRp) of SARS CoV2, and the spike S-protein as potential targets for vaccine development. This review can offer future perspectives for further research and the development of COVID-19 therapies via the design of new drug candidates and multi-epitopic vaccines and through the repurposing of either approved drugs or drugs under clinical trial

Integrative toxicogenomics: Advancing precision medicine and toxicology through artificial intelligence and OMICs technology

More information about a person's genetic makeup, drug response, multi-omics response, and genomic response is now available leading to a gradual shift towards personalized treatment. Additionally, the promotion of non-animal testing has fueled the computational toxicogenomics as a pivotal part of the next-gen risk assessment paradigm. Artificial Intelligence (AI) has the potential to provid new ways analyzing the patient data and making predictions about treatment outcomes or toxicity. As personalized medicine and toxicogenomics involve huge data processing, AI can expedite this process by providing powerful data processing, analysis, and interpretation algorithms. AI can process and integrate a multitude of data including genome data, patient records, clinical data and identify patterns to derive predictive models anticipating clinical outcomes and assessing the risk of any personalized medicine approaches. In this article, we have studied the current trends and future perspectives in personalized medicine & toxicology, the role of toxicogenomics in connecting the two fields, and the impact of AI on personalized medicine & toxicology. In this work, we also study the key challenges and limitations in personalized medicine, toxicogenomics, and AI in order to fully realize their potential

Investigating the Use of Machine Learning Models to Understand the Drugs Permeability Across Placenta

Owing to limited drug testing possibilities in pregnant population, the development of computational algorithms is crucial to predict the fate of drugs in the placental barrier; it could serve as an alternative to animal testing. The ability of a molecule to effectively cross the placental barrier and reach the fetus determines the drug’s toxicological effects on the fetus. In this regard, our study aims to predict the permeability of molecules across the placental barrier. Based on publicly available datasets, several machine learning models are comprehensively analysed across different fingerprints and toolkits to find the best suitable models. Several dataset analysis models are utilised to study the data diversity. Further, this study demonstrates the application of neural network-based models to effectively predict the permeability. K-nearest neighbour (KNN), standard vector classifier (SVC) and Multi-layer perceptron (MLP) are found to be the best-performing models with a prediction percentage of 82%, 86.4% and 90.8%, respectively. Different models are compared to predict the chosen set of drugs, drugs like Aliskiren, some insulin secretagogues and glucocorticoids are found to be negative while predicting the permeability

Micropatterned Neurovascular Interface to Mimic the Blood–Brain Barrier’s Neurophysiology and Micromechanical Function: A BBB-on-CHIP Model

A hybrid blood–brain barrier (BBB)-on-chip cell culture device is proposed in this study by integrating microcontact printing and perfusion co-culture to facilitate the study of BBB function under high biological fidelity. This is achieved by crosslinking brain extracellular matrix (ECM) proteins to the transwell membrane at the luminal surface and adapting inlet–outlet perfusion on the porous transwell wall. While investigating the anatomical hallmarks of the BBB, tight junction proteins revealed tortuous zonula occludens (ZO-1), and claudin expressions with increased interdigitation in the presence of astrocytes were recorded. Enhanced adherent junctions were also observed. This junctional phenotype reflects in-vivo-like features related to the jamming of cell borders to prevent paracellular transport. Biochemical regulation of BBB function by astrocytes was noted by the transient intracellular calcium effluxes induced into endothelial cells. Geometry-force control of astrocyte–endothelial cell interactions was studied utilizing traction force microscopy (TFM) with fluorescent beads incorporated into a micropatterned polyacrylamide gel (PAG). We observed the directionality and enhanced magnitude in the traction forces in the presence of astrocytes. In the future, we envisage studying transendothelial electrical resistance (TEER) and the effect of chemomechanical stimulations on drug/ligand permeability and transport. The BBB-on-chip model presented in this proposal should serve as an in vitro surrogate to recapitulate the complexities of the native BBB cellular milieus