Decoding dynamic interactions between EGFR-TKD and DAC through computational and experimental approaches: A novel breakthrough in lung melanoma treatment
This study focuses on CTX-1, exploring its interaction with the pivotal EGFR-TKD protein, a crucial target in lung cancer therapeutics. A meticulous molecular docking analysis revealed that CTX-1 exhibits a noteworthy binding affinity of -7.9 kcal/mol, challenging Erlotinib, a conventional lung cancer medication, which displayed a binding affinity of -7.3 kcal/mol. For a deeper understanding of CTX-1's molecular mechanics, this study employed rigorous 100-ns molecular dynamics simulations, demonstrating CTX-1's remarkable stability in comparison with erlotinib. The Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBS...
Source: Molecular Medicine - April 30, 2024 Category: Molecular Biology Authors: Rajesh Kumar Meher Showkat Ahmad Mir Kritika Singh Nobendu Mukerjee Binata Nayak Ajoy Kumer Torki A Zughaibi Mohd Shahnawaz Khan Shams Tabrez Source Type: research
Immunopeptidome mining reveals a novel ERS-induced target in T1D
This study provides not only a new explanation for the role of ERS in promoting β-cell-targeted autoimmunity but also a potential target for the prevention and treatment of T1D. The data are available via ProteomeXchange with the identifier PXD041227.PMID:38689020 | DOI:10.1038/s41423-024-01150-0 (Source: Cellular and Molecular Immunology)
Source: Cellular and Molecular Immunology - April 30, 2024 Category: Molecular Biology Authors: Lina Wang Shushu Yang Gaohui Zhu Jie Li Gang Meng Xiaoling Chen Mengjun Zhang Shufeng Wang Xiangqian Li Yu Pan Yi Huang Li Wang Yuzhang Wu Source Type: research
The role of innate lymphoid cells in systemic lupus erythematosus
Cytokine. 2024 Apr 28;179:156623. doi: 10.1016/j.cyto.2024.156623. Online ahead of print.ABSTRACTSystemic lupus erythematosus (SLE) is a connective tissue disorder that affects various body systems. Both the innate and adaptive immunity contribute to the onset and progression of SLE. The main mechanism of SLE is an excessive immune response of immune cells to autoantigens, which leads to systemic inflammation and inflammation-induced organ damage. Notably, a subset of innate immune cells known as innate lymphoid cells (ILCs) has recently emerged. ILCs are pivotal in the early stages of infection; participate in immune resp...
Source: Cytokine - April 30, 2024 Category: Molecular Biology Authors: Yong Chen Xiaotian Gu Kunyu Cao Miao Tu Wan Liu Jiyu Ju Source Type: research
Fundamentals of redox regulation in biology
Nat Rev Mol Cell Biol. 2024 Apr 30. doi: 10.1038/s41580-024-00730-2. Online ahead of print.ABSTRACTOxidation-reduction (redox) reactions are central to the existence of life. Reactive species of oxygen, nitrogen and sulfur mediate redox control of a wide range of essential cellular processes. Yet, excessive levels of oxidants are associated with ageing and many diseases, including cardiological and neurodegenerative diseases, and cancer. Hence, maintaining the fine-tuned steady-state balance of reactive species production and removal is essential. Here, we discuss new insights into the dynamic maintenance of redox homeosta...
Source: Mol Biol Cell - April 30, 2024 Category: Molecular Biology Authors: Helmut Sies Ryan J Mailloux Ursula Jakob Source Type: research
Screening of the effective sites of Cichorium glandulosum against hyperuricemia combined with hyperlipidemia and its network pharmacology analysis
This study aims to explore the pharmacological effects and mechanisms of Cichorium glandulosum on this comorbidity through a combination of animal experiments, network pharmacology, and molecular docking techniques. A rat model of hyperuricaemia combined with hyperlipidaemia was established through a high-fat and high-purine diet, and the effective parts of the aqueous extract of Cichorium glandulosum to reduce uric acid and lipid levels were screened and the components of the parts were analysed by LC-MS/MS. The active components, core targets, and key pathways were analysed using network pharmacology and validated by mol...
Source: Computational Biology and Chemistry - April 30, 2024 Category: Bioinformatics Authors: Zhiguo Yang Bo Lyu Bin Ma Yuefeng Gao Dongmei Qin Source Type: research
Design, synthesis, and biological evaluation of novel 2,3-Di-O-Aryl/Alkyl sulfonate derivatives of l-ascorbic acid: Efficient access to novel anticancer agents via in vitro screening, tubulin polymerization inhibition, molecular docking study and ADME predictions
Bioorg Chem. 2024 Apr 26;147:107402. doi: 10.1016/j.bioorg.2024.107402. Online ahead of print.ABSTRACTA series of novel l-ascorbic acid derivatives bearing aryl and alkyl sulfonate substituents were synthesized and characterized. In vitro anticancer evaluation against MCF-7 (breast) and A-549 (lung) cancer cell lines revealed potent activity for most of the compounds, with 2b being equipotent to the standard drug colchicine against MCF-7 (IC50 = 0.04 μM). Notably, compound 2b displayed 89-fold selectivity for MCF-7 breast cancer over MCF-10A normal breast cells. Derivatives with two sulfonate groups (2a-g, 3a-g) exhibited...
Source: Bioorganic Chemistry - April 30, 2024 Category: Chemistry Authors: Santosh R Deshmukh Archana S Nalkar Aniket P Sarkate Shailee V Tiwari Deepak K Lokwani Shankar R Thopate Source Type: research
Novel guanidine derivatives targeting leukemia as selective Src/Abl dual inhibitors: Design, synthesis and anti-proliferative activity
Bioorg Chem. 2024 Apr 27;147:107410. doi: 10.1016/j.bioorg.2024.107410. Online ahead of print.ABSTRACTA new series of benzene-sulfonamide derivatives 3a-i was designed and synthesized via the reaction of N-(pyrimidin-2-yl)cyanamides 1a-i with sulfamethazine sodium salt 2 as dual Src/Abl inhibitors. Spectral data IR, 1H-, 13C- NMR and elemental analyses were used to confirm the structures of all the newly synthesized compounds 3a-i and 4a-i. Crucially, we screened all the synthesized compounds 3a-i against NCI 60 cancer cell lines. Among all, compound 3b was the most potent, with IC50 of 0.018 μM for normoxia, and 0.001 μ...
Source: Bioorganic Chemistry - April 30, 2024 Category: Chemistry Authors: Amr H Moustafa Asmaa M AboulMagd Ali M Ali Ahmed Khodairy Adel A Marzouk Ayman Nafady Mohamed T M Nemr Source Type: research
Time to switch gears: how long noncoding RNAs function as epigenetic regulators in Apicomplexan parasites
Curr Opin Microbiol. 2024 Apr 29;79:102484. doi: 10.1016/j.mib.2024.102484. Online ahead of print.ABSTRACTLong noncoding RNAs (lncRNA) are emerging as important regulators of gene expression in eukaryotes. In recent years, a large repertoire of lncRNA were discovered in Apicomplexan parasites and were implicated in several mechanisms of gene expression, including marking genes for activation, contributing to the formation of subnuclear compartments and organization, regulating the deposition of epigenetic modifications, influencing chromatin and chromosomal structure and manipulating host gene expression. Here, we aim to u...
Source: Current Opinion in Microbiology - April 30, 2024 Category: Microbiology Authors: Vera Mitesser Karina Simantov Ron Dzikowski Source Type: research
Multiscale biomolecular simulations in the exascale era
Curr Opin Struct Biol. 2024 Apr 29;86:102821. doi: 10.1016/j.sbi.2024.102821. Online ahead of print.ABSTRACTThe complexity of biological systems and processes, spanning molecular to macroscopic scales, necessitates the use of multiscale simulations to get a comprehensive understanding. Quantum mechanics/molecular mechanics (QM/MM) molecular dynamics (MD) simulations are crucial for capturing processes beyond the reach of classical MD simulations. The advent of exascale computing offers unprecedented opportunities for scientific exploration, not least within life sciences, where simulations are essential to unravel intricat...
Source: Current Opinion in Structural Biology - April 30, 2024 Category: Biology Authors: David Carrasco-Busturia Emiliano Ippoliti Simone Meloni Ursula Rothlisberger J ógvan Magnus Haugaard Olsen Source Type: research
Harnessing the 14-3-3 protein-protein interaction network
Curr Opin Struct Biol. 2024 Apr 28;86:102822. doi: 10.1016/j.sbi.2024.102822. Online ahead of print.ABSTRACTProtein-protein interactions (PPIs) play a critical role in cellular signaling and represent interesting targets for therapeutic intervention. 14-3-3 proteins integrate many signaling targets via PPIs and are frequently implicated in disease, making them intriguing drug targets. Here, we review the recent advances in the 14-3-3 field. It will discuss the roles 14-3-3 proteins play within the cell, elucidation of their expansive interactome, and the complex mechanisms that underpin their function. In addition, the rev...
Source: Current Opinion in Structural Biology - April 30, 2024 Category: Biology Authors: Paulo Pitasse-Santos Isaac Hewitt-Richards Malsha D Abeywickrama Wijewardana Sooriyaarachchi Richard G Doveston Source Type: research
Probing allosteric communication with combined molecular dynamics simulations and network analysis
Curr Opin Struct Biol. 2024 Apr 29;86:102820. doi: 10.1016/j.sbi.2024.102820. Online ahead of print.ABSTRACTUnderstanding the allosteric mechanisms within biomolecules involved in diseases is of paramount importance for drug discovery. Indeed, characterizing communication pathways and critical hotspots in signal transduction can guide a rational approach to leverage allosteric modulation for therapeutic purposes. While the atomistic signatures of allosteric processes are difficult to determine experimentally, computational methods can be a remarkable resource. Network analysis built on Molecular Dynamics simulation data is...
Source: Current Opinion in Structural Biology - April 30, 2024 Category: Biology Authors: Mattia Bernetti Stefano Bosio Veronica Bresciani Federico Falchi Matteo Masetti Source Type: research
Integrated Proteomics and Protein Co-expression Network Analysis Identifies Novel Epileptogenic Mechanism in Mesial Temporal Lobe Epilepsy
Mol Neurobiol. 2024 Apr 30. doi: 10.1007/s12035-024-04186-5. Online ahead of print.ABSTRACTOver 50 million people worldwide are affected by epilepsy, a common neurological disorder that has a high rate of drug resistance and diverse comorbidities such as progressive cognitive and behavioural disorders, and increased mortality from direct or indirect effects of seizures and therapies. Despite extensive research with animal models and human studies, limited insights have been gained into the mechanisms underlying seizures and epileptogenesis, which has not translated into significant reductions in drug resistance, morbiditie...
Source: Molecular Medicine - April 30, 2024 Category: Molecular Biology Authors: Arpna Srivastava Priya Rajput Manjari Tripathi Poodipedi Sarat Chandra Ramesh Doddamani Mehar Chand Sharma Sanjeev Lalwani Jyotirmoy Banerjee Aparna Banerjee Dixit Source Type: research
Expression of human dCTP pyrophosphatase 1 (DCTPP1) and its association with cisplatin resistance characteristics in ovarian cancer
In this study, we aimed to understand the role of DCTPP1 in cancer progression and cisplatin response. Using publicly available databases, we analysed the expression and clinical significance of DCTPP1 in ovarian cancer. Our bioinformatics analysis confirmed that DCTPP1 is significantly overexpressed in ovarian cancer and is closely associated with tumour progression and poor prognosis after cisplatin treatment. We also found that DCTPP1 located in oxidoreductase complex and may be involved in various biological processes related to cisplatin resistance, including pyrimidine nucleotide metabolism, the P53 signalling pathwa...
Source: Molecular Medicine - April 30, 2024 Category: Molecular Biology Authors: Yu Wang Xiangyun Chen Qiduan Chen Tiancai Liu Yingsong Wu Liping Huang Yao Chen Source Type: research
Single cell sequencing data identify distinct B cell and fibroblast populations in stricturing Crohn's disease
J Cell Mol Med. 2024 May;28(9):e18344. doi: 10.1111/jcmm.18344.ABSTRACTSingle cell RNA sequencing of human full thickness Crohn's disease (CD) small bowel resection specimens was used to identify potential therapeutic targets for stricturing (S) CD. Using an unbiased approach, 16 cell lineages were assigned within 14,539 sequenced cells from patient-matched SCD and non-stricturing (NSCD) preparations. SCD and NSCD contained identical cell types. Amongst immune cells, B cells and plasma cells were selectively increased in SCD samples. B cell subsets suggested formation of tertiary lymphoid tissue in SCD and compared with NS...
Source: Molecular Medicine - April 30, 2024 Category: Molecular Biology Authors: David T Humphreys Amy Lewis Belen Pan-Castillo Giulio Berti Charles Mein Eva Wozniak Hannah Gordon Radha Gadhok Annamaria Minicozzi Joanna ChinAleong Roger Feakins Eleni Giannoulatou Louisa K James Andrew J Stagg James Oliver Lindsay Andrew Silver Source Type: research
Cutaneous glands of the striped toad, Rhinella crucifer (Wied-Neuwied, 1821) (Amphibia: Bufonidae): Histological study and bioactivities of glandular secretions
This study investigated the morphology of Rhinella crucifer cutaneous glands, as well as the protein/peptide profiles and bioactivities of body gland secretions (BGS) and parotoid macrogland secretions (PS). The parotoid as well as dorsal and ventral skin fragments of male and female individuals were processed for histological analysis. The protein and peptide profiles of male and female gland secretions were evaluated. Male secretions were also assessed for proteolytic, trypsin inhibiting, hemagglutinating, hemolytic, antimicrobial, and anticoagulant activities. The R. crucifer skin structure presented protuberances that ...
Source: Comparative biochemistry and physiology. Part B, Biochemistry and molecular biology. - April 30, 2024 Category: Biochemistry Authors: Gessica Gomes Barbosa Tul íbia Laurindo Silva Ana Patr ícia Silva de Oliveira Th âmarah de Albuquerque Lima Pollyanna Michelle da Silva Carlos Jos é Correia de Santana Jeymesson Raphael Cardoso Vieira Dyeime Ribeiro de Sousa Francisco Assis Leite Souz Source Type: research
