The SGLT2 inhibitor remogliflozin induces vasodilation in the femoral artery of rabbits via activation of a Kv channel, the SERCA pump, and the cGMP signaling pathway.

This study explored the vasodilatory mechanisms of the sodium-glucose cotransporter-2 inhibitor remogliflozin using femoral arteries of rabbits. Remogliflozin dilated femoral arterial rings pre-contracted with phenylephrine in a concentration-dependent manner. Pretreatment with the Ca-sensitive K channel inhibitor (paxilline), the ATP-sensitive K channel inhibitor (glibenclamide), or the inwardly rectifying K channel inhibitor (Ba) did not alter the vasodilatory effect.

Identification of Marine Compounds Inhibiting NF-κBInducing Kinase Through Molecular Docking and Molecular Dynamics Simulations.

NF-κB-inducing kinase (NIK) plays a pivotal role in regulating both the canonical and non-canonical NF-κB signaling pathways, driving the expression of proteins involved in inflammation, immune responses, and cell survival. Overactivation of NIK is linked to various pathological conditions, including chronic inflammation, autoimmune diseases, metabolic disorders, and cancer progression. As such, NIK represents a compelling target for therapeutic intervention in these diseases.

Shared rare genetic variants in multiplex autism families suggest a social memory gene under selection.

Autism spectrum disorder (ASD) affects up to 1 in 59 children, and is one of the most common neurodevelopmental disorders. Recent genomic studies have highlighted the role of rare variants in ASD. This study aimed to identify genes affected by rare variants shared by siblings with ASD and validate the function of a candidate gene FRRS1L.

Discovery of novel TACE inhibitors using graph convolutional network, molecular docking, molecular dynamics simulation, and Biological evaluation.

The increasing utilization of deep learning models in drug repositioning has proven to be highly efficient and effective. In this study, we employed an integrated deep-learning model followed by traditional drug screening approach to screen a library of FDA-approved drugs, aiming to identify novel inhibitors targeting the TNF-α converting enzyme (TACE). TACE, also known as ADAM17, plays a crucial role in the inflammatory response by converting pro-TNF-α to its active soluble form and cleaving other inflammatory mediators, making it a promising target for therapeutic intervention in diseases such as rheumatoid arthritis.

Identification of Malaria-Selective Proteasome β5 Inhibitors Through Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulation.

Malaria remains a global health challenge, with increasing resistance to frontline antimalarial treatments such as artemisinin (ART) threatening the efficacy of current therapies. In this study, we investigated the potential of FDA-approved drugs to selectively inhibit the malarial proteasome, a novel target for antimalarial drug development. By leveraging pharmacophore modeling, molecular docking, molecular dynamics (MD) simulations, and binding free-energy calculations, we screened a library of compounds to identify inhibitors selective for the Plasmodium proteasome over the human proteasome.

Investigating the Inhibitory Potential of Flavonoids against Aldose Reductase: Insights from Molecular Docking, Dynamics Simulations, and gmx_MMPBSA Analysis.

Diabetes mellitus (DM) is a complex metabolic disorder characterized by chronic hyperglycemia, with aldose reductase playing a critical role in the pathophysiology of diabetic complications. This study aimed to investigate the efficacy of flavonoid compounds as potential aldose reductase inhibitors using a combination of molecular docking and molecular dynamics (MD) simulations. The three-dimensional structures of representative flavonoid compounds were obtained from PubChem, minimized, and docked against aldose reductase using Discovery Studio's CDocker module.

Vasorelaxant mechanisms of the antidiabetic anagliptin in rabbit aorta: roles of Kv channels and SERCA pump.

Aims: The present study investigated the vasorelaxant mechanisms of an oral antidiabetic drug, anagliptin, using phenylephrine (Phe)-induced pre-contracted rabbit aortic rings.

Methods: Arterial tone measurement was performed in rabbit thoracic aortic rings.

Results: Anagliptin induced vasorelaxation in a dose-dependent manner.

The antidiabetic drug ipragliflozin induces vasorelaxation of rabbit femoral artery by activating a Kv channel, the SERCA pump, and the PKA signaling pathway.

We explored the vasorelaxant effects of ipragliflozin, a sodium-glucose cotransporter-2 inhibitor, on rabbit femoral arterial rings. Ipragliflozin relaxed phenylephrine-induced pre-contracted rings in a dose-dependent manner. Pre-treatment with the ATP-sensitive K channel inhibitor glibenclamide (10 μM), the inwardly rectifying K channel inhibitor Ba (50 μM), or the Ca-sensitive K channel inhibitor paxilline (10 μM) did not influence the vasorelaxant effect.

Drug Repositioning via Graph Neural Networks: Identifying Novel JAK2 Inhibitors from FDA-Approved Drugs through Molecular Docking and Biological Validation.

The increasing utilization of artificial intelligence algorithms in drug development has proven to be highly efficient and effective. One area where deep learning-based approaches have made significant contributions is in drug repositioning, enabling the identification of new therapeutic applications for existing drugs. In the present study, a trained deep-learning model was employed to screen a library of FDA-approved drugs to discover novel inhibitors targeting JAK2.

Enhancing malaria detection in resource-limited areas: A high-performance colorimetric LAMP assay for Plasmodium falciparum screening.

Malaria eradication efforts in resource-limited areas require a rapid, economical, and accurate tool for detecting of the low parasitemia. The malaria rapid diagnostic test (mRDT) is the most suitable for on-site detection of the deadliest form of malaria, Plasmodium falciparum. However, the deletions of histidine rich protein 2 and 3 genes are known to compromise the effectiveness of mRDT.

Functional characterization of hexose transporter 1.

is the most widely distributed human malaria parasite. The eradication of vivax malaria remains challenging due to transmission of drug-resistant parasite and dormant liver form. Consequently, anti-malarial drugs with novel mechanisms of action are urgently demanded.

Merozoite surface protein 1 paralog is involved in the human erythrocyte invasion of a zoonotic malaria, .

The zoonotic malaria parasite is an important public health concern in Southeast Asia. Invasion of host erythrocytes is essential for parasite growth, and thus, understanding the repertoire of parasite proteins that enable this process is vital for identifying vaccine candidates and how some species are able to cause zoonotic infection. Merozoite surface protein 1 (MSP1) is found in all malaria parasite species and is perhaps the most well-studied as a potential vaccine candidate.

Discovery of GABA Aminotransferase Inhibitors via Molecular Docking, Molecular Dynamic Simulation, and Biological Evaluation.

γ-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that degrades γ-aminobutyric (GABA) in the brain. GABA is an important inhibitory neurotransmitter that plays important neurological roles in the brain. Therefore, GABA-AT is an important drug target that regulates GABA levels.

Functional characterization of Clonorchis sinensis choline transporter.

Clonorchis sinensis is commonly found in East Asian countries. Clonorchiasis is prevalent in these countries and can lead to various clinical symptoms. In this study, we used overlap extension polymerase chain reaction (PCR) and the Xenopus laevis oocyte expression system to isolate a cDNA encoding the choline transporter of C.

Plasmodium vivax merozoite-specific thrombospondin-related anonymous protein (PvMTRAP) interacts with human CD36, suggesting a novel ligand-receptor interaction for reticulocyte invasion.

Background: The Plasmodium vivax merozoite restrictively invades immature erythrocytes, suggesting that its ligand(s) might interact with corresponding receptor(s) that are selectively abundant on reticulocytes to complete the invasion. Finding the ligand‒receptor interaction involved in P. vivax invasion is critical to vivax malaria management; nevertheless, it remains to be unraveled.

Caffeic acid methyl ester inhibits LPS‑induced inflammatory response through Nrf2 activation and NF‑κB inhibition in human umbilical vein endothelial cells.

Caffeic acid (CA) derivatives have been reported to exert anti-inflammatory activities in various inflammatory conditions. However, the impact of CA methyl ester (CAME) on the inflammatory response in vascular endothelial cells has not been thoroughly elucidated. In the present study, the aim was to understand how CAME can reduce inflammation in human umbilical vein endothelial cells (HUVECs), which were challenged with lipopolysaccharide (LPS), and elucidate its mechanisms.

Machine Learning-Based Drug Repositioning of Novel Janus Kinase 2 Inhibitors Utilizing Molecular Docking and Molecular Dynamic Simulation.

Machine learning algorithms have been increasingly applied in drug development due to their efficiency and effectiveness. Machine learning-based drug repurposing can contribute to the identification of novel therapeutic applications for drugs with other indications. The current study used a trained machine learning model to screen a vast chemical library for new JAK2 inhibitors, the biological activities of which were reported.