Predictive Modelling in pharmacokinetics: from in-silico simulations to personalized medicine.

INTRODUCTION: Pharmacokinetic parameters assessment is a critical aspect of drug discovery and development, yet challenges persist due to limited training data. Despite advancements in machine learning and in-silico predictions, scarcity of data hampers accurate prediction of drug candidates' pharmacokinetic properties. AREAS COVERED: The study highlights current developments in human pharmacokinetic prediction, talks about attempts to apply synthetic approaches for molecular design, and searches several databases, including Scopus, PubMed, Web of Science, and Google Scholar. The article stresses importance of rigorous analysis of machine learning model performance in assessing progress and explores molecular modeling (MM) techniques, descriptors, and mathematical approaches. Transitioning to clinical drug development, article highlights AI (Artificial Intelligence) based computer models optimizing trial design, patient selection, dosing strategies, and biomarker identification. In-silico models, including molecular interactomes and virtual patients, predict drug performance across diverse profiles, underlining the need to align model results with clinical studies for reliability. Specialized training for human specialists in navigating predictive models is deemed critical. Pharmacogenomics, integral to personalized medicine, utilizes predictive modeling to anticipate patient responses, contributing to more efficient healthcare system. Challenges in realizing potential of predictive modeling, including ethical considerations and data privacy concerns, are acknowledged. EXPERT OPINION: AI models are crucial in drug development, optimizing trials, patient selection, dosing, and biomarker identification and hold promise for streamlining clinical investigations.

Revisiting the Mitochondrial Function and Communication in Neurodegenerative Diseases.

Neurodegenerative disorders are distinguished by the progressive loss of anatomically or physiologically relevant neural systems. Atypical mitochondrial morphology and metabolic malfunction are found in many neurodegenerative disorders. Alteration in mitochondrial function can occur as a result of aberrant mitochondrial DNA, altered nuclear enzymes that interact with mitochondria actively or passively, or due to unexplained reasons. Mitochondria are intimately linked to the Endoplasmic reticulum (ER), and ER-mitochondrial communication governs several of the physiological functions and procedures that are disrupted in neurodegenerative disorders. Numerous researchers have associated these disorders with ER-mitochondrial interaction disturbance. In addition, aberrant mitochondrial DNA mutation and increased ROS production resulting in ionic imbalance and leading to functional and structural alterations in the brain as well as cellular damage may have an essential role in disease progression via mitochondrial malfunction. In this review, we explored the evidence highlighting the role of mitochondrial alterations in neurodegenerative pathways in most serious ailments, including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD).

Isolation, Production, and Characterization of Serum Immunoglobulin M (IgM) of Indian Major Carp Cirrhinus mrigal (MRIGAL).

A method for the isolation of immunoglobulin M (IgM) in Indian major carp Cirrhinus mrigal (mrigal) serum to produce polyclonal antibodies is described in the present study. The purified immunoglobulins (IgM) were isolated from the serum of mrigal (Cirrhinus mrigal) by the bovine serum albumin (BSA)-CL affinity column purification method, and the IgM was used to produce a polyclonal rabbit anti-mrigal IgM antiserum. The IgM preparations were employed in the characterization of mrigal serum immunoglobulin. Reduced mrigal IgM on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was shown to consist of two subunits, compatible with heavy and light chains. A single heavy chain at approximately 90 kDa and variant of light chain 30 kDa were found. The dominant form of nonreduced IgM had a MW of approximately 900 kDa, suggesting a tetrameric structure based on estimated molecular weights, the relative protein content, and the reactivity with anti-mrigal IgM antisera, was obtained. The antisera were characterized as to specificity and reactivity by means of the enzyme linked immuno-sorbent assay (ELISA) and western blotting method. The information on the structure and character of immunoglobulin of fishes is essential in health management. The study described here investigates the possibility of using the serological techniques to assess the reactivity of antibody with the anti-mrigal IgM antisera.

Artocarpus hirsutus Lam Leaf Extract-Evaluation of Analgesic and Anti-Inflammatory Activity.

The study involved extraction, identification, and evaluation of pharmacological activities of the phytochemicals present. Artocarpus hirsutus Lam, commonly known as Wild jack is a greatly valued medicinal plant, which belongs to the plant family Moraceae. Preliminary phytochemical screening studies indicated the presence of flavonoids, saponins, tannins, glycosides, and alkaloids. This study estimated the analgesic and anti-inflammatory prospective of ethanolic leaf extract of Artocarpus hirsutus Lam. The findings showed that at various doses of 100, 200, and 400 mg/kg body weight when administered orally to rats, analgesic effects were produced, also the anti-inflammatory effect studied by carrageenan-induced rat paw edema test showed major anti-inflammatory action. The result indicates that the leaf extract of Artocarpus hirsutus Lam possesses major analgesic and anti-inflammatory activity and therefore requires further investigations to better understand the mechanism of action.