Опубликована: Сен. 18, 2024
Язык: Английский
Nature Chemistry, Год журнала: 2025, Номер unknown
Опубликована: Янв. 13, 2025
Abstract Understanding the dynamics of membrane protein–ligand interactions within a native lipid bilayer is major goal for drug discovery. Typically, cell-based assays are used, however, they often blind to effects protein modifications. In this study, using archetypal G protein-coupled receptor rhodopsin, we found that and its effectors can be released directly from retina rod disc membranes infrared irradiation in mass spectrometer. Subsequent isolation dissociation by multiphoton enabled sequencing individual proteoforms. Specifically, categorized distinct proteoforms localized labile palmitoylations, discovered Gβγ proteoform abolishes association defined modifications on proteins influence their assembly. Given reports undesirable side-effects involving vision, characterized off-target binding two phosphodiesterase 5 inhibitors, vardenafil sildenafil, 6 (PDE6). The results demonstrate differential reactivity with PDE6 an interaction preference lipidated proteins. summary, study highlights opportunities probing proteoform–ligand natural environments.
Язык: Английский
Процитировано
2
The EPMA Journal, Год журнала: 2024, Номер 15(3), С. 525 - 544
Опубликована: Июль 13, 2024
Язык: Английский
Процитировано
6
Proteomes, Год журнала: 2024, Номер 12(2), С. 14 - 14
Опубликована: Апрель 19, 2024
With growing recognition and acknowledgement of the genuine complexity proteomes, we are finally entering post-proteogenomic era. Routine assessment proteomes as inferred correlates gene sequences (i.e., canonical ‘proteins’) cannot provide necessary critical analysis systems-level biology that is needed to understand underlying molecular mechanisms pathways or identify most selective biomarkers therapeutic targets. These requirements demand at level proteoforms/protein species, actual active players. Currently, only highly refined integrated integrative top-down proteomics (iTDP) enables analytical depth routine, comprehensive, quantitative proteome assessments across widest range proteoforms inherent native systems. Here a broad perspective field, taking in historical current realities, establish more balanced understanding where field has come from (in particular during ten years since Proteomes was launched), issues, how things likely need proceed if deep analyses succeed. We base this our firm belief best proteomic reflect, closely possible, sample moment sampling. also seek emphasise future approaches based on exploitation complementarity currently successful approaches. This emphasises continuously evaluate further optimize established approaches, avoid complacency thinking expectations but promote careful development introduction new notably those address proteoforms. Above all, wish rigorous focus quality must override largely values speed; latter would certainly be nice, could thus effectively, routinely, quantitatively assessed. Alas, composed proteoforms, not species can amplified directly mirror genes ‘canonical’). The problem hard, accept it such, payoff playing longer game promise far biomarkers, drug targets, truly personalised even individualised medicine.
Язык: Английский
Процитировано
5
ACS Infectious Diseases, Год журнала: 2024, Номер 10(8), С. 2485 - 2506
Опубликована: Июль 13, 2024
Leishmaniasis, a critical Neglected Tropical Disease caused by Leishmania protozoa, represents significant global health risk, particularly in resource-limited regions. Conventional treatments are effective but suffer from serious limitations, such as toxicity, prolonged treatment courses, and rising drug resistance. Herein, we highlight the potential of inorganic nanomaterials an innovative approach to enhance Leishmaniasis therapy, aligning with One Health concept considering these treatments' environmental, veterinary, public impacts. By leveraging adjustable properties nanomaterials─including size, shape, surface charge, tailored for various diseases can be developed that less harmful environment nontarget species. We review recent advances metal-, oxide-, carbon-based combating examining their mechanisms action dual use standalone or delivery systems. Our analysis highlights promising yet underexplored frontier employing materials more holistic disease management.
Язык: Английский
Процитировано
4
The EPMA Journal, Год журнала: 2025, Номер unknown
Опубликована: Янв. 16, 2025
Язык: Английский
Процитировано
0
IGI Global eBooks, Год журнала: 2025, Номер unknown, С. 275 - 310
Опубликована: Фев. 5, 2025
The integration of Artificial Intelligence (AI), Machine Learning (ML), and Big Data is transitioning the pharmaceutical industry, specifically in drug discovery, process optimization, clinical development. This revolution enhances target identification through advanced data analytics, empowering discovery novel biomarkers compounds. AI-driven high-throughput virtual screening methods accelerate promising candidates, while predictive modeling improves accuracy efficacy predictions. In manufacturing, AI optimizes supply chain management quality control real-time monitoring maintenance, ensuring efficient production processes.
Язык: Английский
Процитировано
0
Drug Development Research, Год журнала: 2025, Номер 86(3)
Опубликована: Апрель 26, 2025
ABSTRACT Recent advances in pharmacology are revolutionizing drug discovery and treatment strategies through personalized medicine, pharmacogenomics, artificial intelligence (AI). The objective of the present study is to review role AI‐based optimizing patient outcomes with improved efficacy reduced side effects. A comprehensive was performed debate utility pharmacogenomics prediction response, AI discovery, medicine clinic. This highlights how techniques evolving aid AI. Personalized makes fit DNA pattern for higher minimal Pharmacogenomics forecasts action a terms genetic difference. speeds up enhance effectiveness accuracy finding evaluating leads. Studies show that customized charts therapy an individual patient's profile, resulting better therapy. facilitates precise selection by considering variations, reducing adverse reactions. applying predictive modeling data‐driven evaluation propel optimized development pathways. Together, these enabling more efficient safer practices across medical disciplines. combination pharmacology, genomics, contemporary healthcare personalization treatments, safety, therapeutic outcomes. future research should be on overcoming ethical regulatory issues facilitate broader clinical implementation.
Язык: Английский
Процитировано
0
Cancer Treatment and Research Communications, Год журнала: 2024, Номер 42, С. 100860 - 100860
Опубликована: Янв. 1, 2024
The incidence of cancer continues to increase worldwide, resulting in significant physical, emotional, and financial challenges for individuals, families, communities, healthcare systems. Cancer is projected be responsible approximately 10 million deaths 2020, accounting one six globally. Prostate, colon, lung, breast cancers are the most common types cancer. In India, it estimated that there will around 2.7 patients by 2020. Personalized medicine has potential offer an alternative approach treatment. Precision medicine, often known as personalized a new treatment technique focuses on tailoring medication each patient's specific genetic, biochemical, lifestyle factors. goal optimize tumor response while minimizing therapy side effects, improved patient care quality life. allows creation focused medicines address gene mutations leveraging knowledge about cancer, including its genetic makeup. Ongoing research seeks detect modifications diverse types, produce novel diagnostic tools, develop treatments particularly target these changes. recent years, achieved major advances solid tumors, with promise improve precision, reduce well enhance outcomes therapy. This review aims objectively evaluate transformation treatment, emphasizing shift towards more precise methodology.
Язык: Английский
Процитировано
3
Опубликована: Апрель 29, 2024
Many ailments can be diagnosed while they are asymptomatic, meaning that the patient has no signs or symptoms of a progressing disease. If caught in their initial stage formation, these maladies effectively treated, leading to successful outcomes; curative therapies halt illnesses from advancing, thus improving quality life, and long-term survival patient. Still cutting-edge upgrades precision technologies necessary for early, reliable, affordable, rapid disease detection, but also vital well-being people future global public health. The emerging role utility non-invasive repeatable diagnostic test approaches detection health conditions been liquid biopsies based on genomic biomarkers. As such, biological fluids permit any measurable molecular indicator signature (e.g., proteins), provide valuable information individual’s wellness and/or Among bodily secretions used diagnostics is sputum, complex viscous gel-like biopolymeric network, gained growing recognition as rich source biomarkers airway infections, pulmonary diseases, serves determinant reveal other illnesses. per World Health Organization, burden respiratory exacerbated by factors, ranging considerable subjection air pollution occupational contaminants, tobacco smoking second-hand smoke, addition poor socio-economic status. Due likely increase determinants, tract rise, affecting many individuals, putting stress healthcare facilities services worldwide. We therefore highlight need use expectorated induced sputum specimens routine sample testing protein diagnose chronic maladies, predict inflammation progression, well monitor effectiveness treatments. Further, we discuss urgency fast reliable point-of-care methods detect quantify crucial specimens, limitations faced when dealing with matrices.
Язык: Английский
Процитировано
2
The EPMA Journal, Год журнала: 2024, Номер 15(2), С. 345 - 373
Опубликована: Май 24, 2024
Язык: Английский
Процитировано
2