Biomolecules最新文献

{"title":"Ensemble-Based Binding Free Energy Profiling and Network Analysis of the KRAS Interactions with DARPin Proteins Targeting Distinct Binding Sites: Revealing Molecular Determinants and Universal Architecture of Regulatory Hotspots and Allosteric Binding.","authors":"Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady Verkhivker","doi":"10.3390/biom15060819","DOIUrl":"10.3390/biom15060819","url":null,"abstract":"<p><p>KRAS is a pivotal oncoprotein that regulates cell proliferation and survival through interactions with downstream effectors such as RAF1. Despite significant advances in understanding KRAS biology, the structural and dynamic mechanisms of KRAS allostery remain poorly understood. In this study, we employ microsecond molecular dynamics simulations, mutational scanning, and binding free energy calculations together with dynamic network modeling to dissect how engineered DARPin proteins K27, K55, K13, and K19 engage KRAS through diverse molecular mechanisms ranging from effector mimicry to conformational restriction and allosteric modulation. Mutational scanning across all four DARPin systems identifies a core set of evolutionarily constrained residues that function as universal hotspots in KRAS recognition. KRAS residues I36, Y40, M67, and H95 consistently emerge as critical contributors to binding stability. Binding free energy computations show that, despite similar binding modes, K27 relies heavily on electrostatic contributions from major binding hotspots while K55 exploits a dense hydrophobic cluster enhancing its effector-mimetic signature. The allosteric binders K13 and K19, by contrast, stabilize a KRAS-specific pocket in the α3-loop-α4 motif, introducing new hinges and bottlenecks that rewire the communication architecture of KRAS without full immobilization. Network-based analysis reveals a strikingly consistent theme: despite their distinct mechanisms of recognition, all systems engage a unifying allosteric architecture that spans multiple functional motifs. This architecture is not only preserved across complexes but also mirrors the intrinsic communication framework of KRAS itself, where specific residues function as central hubs transmitting conformational changes across the protein. By integrating dynamic profiling, energetic mapping, and network modeling, our study provides a multi-scale mechanistic roadmap for targeting KRAS, revealing how engineered proteins can exploit both conserved motifs and isoform-specific features to enable precision modulation of KRAS signaling in oncogenic contexts.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical and Functional Characterization of <i>E. coli</i> Aminopeptidase N: A New Role as a 6-Monoacetylmorphine Hydrolase.","authors":"Xiabin Chen, Yishuang Li, Jianzhuang Yao, Xiaoxuan Li, Hualing Li, Zelin Wu, Qi Hu, Nuo Xu, Tingjun Hou, Jiye Wang, Shurong Hou","doi":"10.3390/biom15060822","DOIUrl":"10.3390/biom15060822","url":null,"abstract":"<p><p>6-monoacetylmorphine (6-MAM), a primary active metabolite of heroin that reaches the human brain, plays a crucial role in producing heroin-associated physiological and lethal effects. Therefore, 6-MAM has emerged as a key target for alleviating the adverse consequences of heroin abuse. In this study, the proposed 6-MAM hydrolase <i>E. coli</i> aminopeptidase N (eAPN) was recombinantly produced, and its biochemical and functional profiles were investigated. eAPN's biochemical properties, with respect to pH, metal ions, and temperature, and catalytic functions toward peptidase substrates and 6-MAM were thoroughly examined. Extensive experiments reveal that incorporation of an N-terminal His-tag notably affects eAPN's aminopeptidase activity. This cost-effective recombinant eAPN exhibits favorable thermostability and optimal activity at pH 7.5. Kinetic analysis toward peptidase substrates reveals that eAPN preferentially cleaves peptides following amino acid residues in the order of Ala > Arg >> Met, Gly > Leu > Pro, indicating a preference for small or basic amino acid residues as substrates. Computational and experimental studies have, for the first time, discovered that eAPN is capable of catalyzing the hydrolysis of heroin and 6-MAM, which has shed light on its functional versatility and potential applications. This work elucidates the biochemical properties of eAPN and expands its catalytic functions, thereby laying the groundwork for a deep understanding and further reengineering of eAPN to enhance its activity toward 6-MAM for heroin detoxification.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial and Antiradical Activity of Extracts from Leaves of Various Cultivars of <i>Pyrus communis</i> and <i>Pyrus pyrifolia</i>.","authors":"Beata Żbikowska, Magdalena Kotowska, Andrzej Gamian, Katarzyna Patek, Katarzyna Matuła, Daria Augustyniak, Kamila Korzekwa, Zbigniew Sroka","doi":"10.3390/biom15060821","DOIUrl":"10.3390/biom15060821","url":null,"abstract":"<p><p>Certain plant raw materials are rich in antioxidant and antimicrobial compounds, which are highly valued in modern medicine. These include the leaves of various species and cultivars of pears. For our research, we chose the leaves of the common pear (<i>Pyrus communis</i>) and Asian pear (<i>Pyrus pyrifolia</i>). Four different extracts were obtained from all raw materials and were investigated for their antimicrobial and antioxidant activity. The content of total phenolics and flavonoids was measured using colorimetric methods, and antiradical activity was measured using DPPH and ABTS radical probes. The antimicrobial activity of extracts was measured using the disc diffusion method, and the amount of major antimicrobial components (hydroquinone and arbutin) was measured using the HPLC method. The highest amount of general phenols and flavonoids was found in ethyl acetate extracts in all cultivars, and the lowest amount of phenols was found in the remaining aqueous solution. The amount of general phenols positively correlated with the antiradical activity of extracts. The strongest antimicrobial activity against Gram-positive and Gram-negative pathogens corresponded to the highest content of hydroquinone and arbutin in ethyl acetate extracts. Extracts obtained from pear leaves showed an average content of phenolic compounds and average antiradical activity compared to extracts from other raw materials, especially green tea or bergenia leaves. The amount of hydroquinone was moderate, lower than that of arbutin. The antimicrobial activity of the extracts was moderate due to the average amount of hydroquinone, which is the main antimicrobial compound.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterostilbene Carbamates with Selective and Remarkable Butyrylcholinesterase Inhibition: Computational Study and Physico-Chemical Properties.","authors":"Anamarija Raspudić, Ilijana Odak, Milena Mlakić, Antonija Jelčić, Karla Bulava, Karla Karadža, Valentina Milašinović, Ivana Šagud, Paula Pongrac, Dora Štefok, Danijela Barić, Irena Škorić","doi":"10.3390/biom15060825","DOIUrl":"10.3390/biom15060825","url":null,"abstract":"<p><p>This manuscript reports the synthesis and characterization of 19 novel heterostilbene carbamates, designed as selective butyrylcholinesterase (BChE) inhibitors with potential applications in the treatment of neurodegenerative disorders, particularly Alzheimer's disease. The compounds were synthesized from resveratrol analogs, and their structures were confirmed by NMR spectroscopy, high-resolution mass spectrometry (HRMS), and single-crystal X-ray diffraction for selected derivatives (compounds <b>1</b> and <b>4</b>). In vitro assays demonstrated high selectivity toward BChE over acetylcholinesterase (AChE), with compound <b>16</b> exhibiting exceptional inhibitory activity (IC₅₀ = 26.5 nM). Furthermore, compound <b>16</b> showed moderate anti-inflammatory effects by inhibiting LPS-stimulated TNF-α production in peripheral blood mononuclear cells. In silico ADME(T) profiling revealed favorable pharmacokinetic properties and low mutagenic potential for the majority of compounds. Molecular docking and molecular dynamics simulations confirmed stable binding interactions within the BChE active site. These results highlight heterostilbene carbamates as promising lead structures for developing novel therapeutic agents targeting neurodegenerative diseases.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the Adiponectin Hallmark and Exploring the Therapeutic Potential of Its Receptor Agonists in Cancer Metabolic Reprogramming.","authors":"Sanober Kafeel, Giuseppina Palmiero, Alessia Salzillo, Angela Ragone, Silvio Naviglio, Luigi Sapio","doi":"10.3390/biom15060820","DOIUrl":"10.3390/biom15060820","url":null,"abstract":"<p><p>As the most abundant fat-derived hormone, adiponectin plays an essential role in regulating energy homeostasis. Current evidence proposes the serum levels of adiponectin as a risk factor and a diagnostic/prognostic biomarker in cancer. Moreover, distinctive antineoplastic features have also been reported as a result of adiponectin supplementation in preclinical models. Mapping of the cancer-associated metabolic changes has elucidated a highly adaptable and interconnected system that allows malignant cells to sustain their growth and survival. Along with the pyruvate into acetyl-CoA conversion, downregulation of both lactate dehydrogenase and glycolysis-related genes depicts the main adiponectin-induced perturbations affecting glucose metabolism in cancer. Meanwhile, a multi-level approach involving lipid trafficking, catabolism, and de novo synthesis has been attributed to adiponectin in malignancies. The adiponectin receptor agonist AdipoRon has recently been recognized as a promising antineoplastic compound. Remarkably, AdipoRon-mediated changes in cancer metabolism occur together with its antiproliferative potential. This review aimed at recapitulating the modulatory effects of adiponectin, as well as those of its synthetic receptor agonists, in driving metabolic alterations in cancerous cells. A critical discussion is also conducted to deduce whether the adiponectin axis could serve as a putative target to address the metabolic reprogramming in cancer progression.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antechodynamics and Antechokinetics: Dynamics and Kinetics of Antibiotic Resistance Biomolecules.","authors":"F Baquero, R Cantón, A E Pérez-Cobas, T M Coque, B Levin, J Rodríguez-Beltrán","doi":"10.3390/biom15060823","DOIUrl":"10.3390/biom15060823","url":null,"abstract":"<p><p>The pharmacology of antimicrobial agents comprises pharmacodynamics and pharmacokinetics. Pharmacodynamics refers to studying drugs' mode of action on their molecular targets at various concentrations and the resulting effect(s). Pharmacokinetics refers to studying the way(s) in which drugs enter the body and are distributed to their targets in various compartments (such as tissues) and how local drug concentrations are modified in time, such as by metabolism or excretion. Pharmacodynamics and pharmacokinetics constitute pivotal knowledge for establishing the breakpoints used to identify the appropriate antimicrobial agents for infection therapy. Antibiotic resistance is the biological force opposing antimicrobials' pharmacological effects. However, we do not have a term similar to pharmacology for microbial antibiotic resistance reactions. Here, we propose the new scientific field of antechology (from the classic Greek <i>antechó</i>, resistance), studying the dynamics and kinetics of antibiotic resistance molecules which oppose the effect of antimicrobial drugs. Antechodynamics refers to the study of the molecular mechanisms through which antibiotic molecules are chemically modified or degraded by particular bacterial resistance enzymes (primary effectors) or drive the modification of an antibiotic's target inhibition sites through molecules released by antibiotic action on the microorganism (secondary effectors). Antechokinetics refers to the study of the processes leading to bacterial spatial cellular (subcellular, pericellular, extracellular) localizations of the molecules involved in antibiotic detoxifying mechanisms. Molecules' local concentrations change over time due to their production, their degradation, and ultimately their excretion rates. We will examine the antechodynamics and antechokinetics for various antimicrobial classes and the relation between pharmacodynamics/pharmacokinetics and antechodynamics/antechokinetics.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role and Pathogenesis of Tau Protein in Alzheimer's Disease.","authors":"Xiaoyue Hong, Linshu Huang, Fang Lei, Tian Li, Yi Luo, Mengliu Zeng, Zhuo Wang","doi":"10.3390/biom15060824","DOIUrl":"10.3390/biom15060824","url":null,"abstract":"<p><p>Alzheimer's disease (AD), a predominant neurodegenerative disorder, is clinically characterized by progressive cognitive deterioration and behavioral deficits. An in-depth understanding of the pathogenesis and neuropathology of AD is essential for the development of effective treatments and early diagnosis techniques. The neuropathological signature of AD involves two hallmark lesions: intraneuronal neurofibrillary tangles composed of hyperphosphorylated tau aggregates and extracellular senile plaques containing amyloid-β (Aβ) peptide depositions. Although Aβ-centric research has dominated AD investigations over the past three decades, pharmacological interventions targeting Aβ pathology have failed to demonstrate clinical efficacy. Tau, a microtubule-associated protein predominantly localized to neuronal axons, orchestrates microtubule stabilization and axonal transport through dynamic tubulin interactions under physiological conditions. In AD pathogenesis, however, tau undergoes pathogenic post-translational modifications (PTMs), encompassing hyperphosphorylation, lysine acetylation, methylation, ubiquitination, and glycosylation. These PTM-driven alterations induce microtubule network disintegration, mitochondrial dysfunction, synaptic impairment, and neuroinflammatory cascades, ultimately culminating in irreversible neurodegeneration and progressive cognitive decline. This review synthesizes contemporary advances in tau PTM research and delineates their mechanistic contributions to AD pathogenesis, thereby establishing a framework for biomarker discovery, targeted therapeutic development, and precision medicine approaches in tauopathies. This review synthesizes contemporary advances in tau PTM research and delineates their mechanistic contributions to AD pathogenesis, thereby establishing a solid theoretical and experimental basis for the early diagnosis of neurodegenerative diseases, the discovery of therapeutic targets, and the development of novel therapeutic strategies.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in SELEX Technology for Aptamers and Emerging Applications in Therapeutics and Drug Delivery.","authors":"Liangjie Feng, Yu Sun, Wenshen Jia, Yang Yu, Chang Liu, Jing Yang, Yunxia Luan, Jin Chen, Fengchao Wang","doi":"10.3390/biom15060818","DOIUrl":"10.3390/biom15060818","url":null,"abstract":"<p><p>Nucleic acid aptamers, selected through the Systematic Evolution of Ligands by Exponential Enrichment (SELEX), are short nucleic acid sequences that exhibit high affinity and specificity towards diverse targets. Over the past three decades, substantial advancements have been made in both the technology and applications of nucleic acid aptamers. This review provides an in-depth analysis of the historical development and defining characteristics of aptamers, highlighting recent technological innovations in SELEX, including Capillary Electrophoresis SELEX, Microfluidic SELEX, Cell-SELEX, and others. We explore the applications of aptamers in therapeutic and targeted drug delivery, emphasizing their advantages over traditional antibodies such as cost-effectiveness, ease of synthesis, and lower immunogenicity. Key challenges such as stability, specificity, and efficient delivery are discussed, with proposed strategies for improvement including advanced chemical modifications and integration with nanotechnology. By integrating advanced technologies, aptamers hold significant promise for enhancing precision medicine and personalized therapeutic interventions, offering new avenues for the treatment of complex diseases.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proton-Sensing G Protein-Coupled Receptors and Their Potential Role in Exercise Regulation of Arterial Function.","authors":"Fengzhi Yu, Dandan Jia, Ru Wang","doi":"10.3390/biom15060813","DOIUrl":"10.3390/biom15060813","url":null,"abstract":"<p><p>During periods of exercise, the primary cause of metabolic acidosis is the accumulation of lactate from anaerobic metabolism, whereas a transient increase in CO₂ triggers a mild respiratory acidosis through the production of carbonic acid (H₂CO₃). The combined effects of these reactions result in a slight acidifying shift in arterial blood pH. Proton-sensing G protein-coupled receptors (including GPR68, GPR4, GPR132, and GPR65) represent the primary receptors within the body for detecting alterations in extracellular proton concentrations. These receptors have been demonstrated to possess potential roles in mechanosensation, intestinal inflammation, oncoimmunological interactions, hematopoiesis, as well as inflammatory and neuropathic pain. Recent studies have shown that the activation or inhibition of these receptors modulates a number of arterial functions, including angiogenesis, arterial relaxation, and arterial inflammation. It is well established that moderate exercise has a beneficial effect on the regulation of arterial function. This study examines the effect of exercise on proton concentrations in the microenvironment of the organism and its influence on proton-sensing G protein-coupled receptors located on cell membranes, as well as possible mechanisms involved in the regulation of arterial function. The objective is to present novel perspectives for the exploration of potential drug targets for the prevention and treatment of arterial dysfunction and the development of exercise regimens.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Innate Immunity Mediated by IL-36α in Atopic Dermatitis and Differences in Cytokine Profiles of Lymphocytes in the Skin and Draining Lymph Nodes.","authors":"Ayaka Ichikawa, Mai Nishimura, Masako Ichishi, Yasutomo Imai, Yoshiaki Matsushima, Yoichiro Iwakura, Masatoshi Watanabe, Kiyofumi Yamanishi, Keiichi Yamanaka","doi":"10.3390/biom15060817","DOIUrl":"10.3390/biom15060817","url":null,"abstract":"<p><p>(1) Background: The IL-36 cytokines have been identified as key contributors to pustular psoriasis, and their inhibitor is already in clinical use. However, few studies have explored them in atopic dermatitis. (2) Methods: The role of IL-36α was investigated in various atopic dermatitis models using wild-type, keratin 14-specific IL-33 transgenic, IL-18 transgenic, caspase-1 transgenic, and caspase-1 transgenic mice with IL-17AF deletion, reflecting diverse aspects of human skin inflammation. IL-36α was administered subcutaneously in five doses on alternate days across the five strains to examine cellular infiltration patterns and cytokine expression levels. (3) Results: The skin phenotype was exacerbated, accompanied by worsening edema and skin thickness in all mouse groups upon IL-36α administration. An increase in infiltrating cells was observed among innate immune cells, while lymphocyte counts, including T cells and innate lymphoid cells, did not rise. Additionally, anti-inflammatory cytokines were induced simultaneously with inflammatory cytokines and downstream cytokines of IL-36α as well. Infiltrating lymphocytes in the skin displayed a distinct Type 2 cytokine-dominant profile for innate lymphoid cells and a Type 3 cytokine-dominant profile for T helper cells and γδ T cells, contrasting with the Type 1-dominant cell profile in draining lymph nodes. Type 1, Type 2, and Type 3 cytokine dominance patterns were not affected by the administration of IL-36α. (4) Conclusions: IL-36α triggers inflammatory responses in atopic dermatitis by activating innate immunity. The infiltrating lymphocytes in the skin have different cytokine production profiles between innate lymphoid cells and T cells, as well as different patterns of cytokine production in their draining lymph nodes.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 6","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}