Biomolecules最新文献

{"title":"Polysaccharide Peptide from <i>Ganoderma lucidum</i> Reduces Acute Kidney Injury Through Regulating the Integrin β3/Fn1 Axis.","authors":"Hatungimana Mediatrice, Hongjian Luo, Lianfu Wang, Yang Yao, Zhujun Liu, Nsanzinshuti Aimable, Yingping Hu, Yukun Zhang, Zhanxi Lin, Dongmei Lin","doi":"10.3390/biom16040610","DOIUrl":"10.3390/biom16040610","url":null,"abstract":"<p><p>Acute kidney injury (AKI) continues to pose a significant clinical challenge due to its high morbidity rates and limited therapeutic options. Recent evidence suggests that natural compounds may provide renoprotective benefits by modulating oxidative stress and inflammation. This study examines the protective effects of a novel polysaccharide peptide extracted from Ganoderma lucidum (GL-PPQ1) against renal ischemia-reperfusion (I/R) injury, with particular emphasis on the integrin β3/Fibronectin 1 (Fn1) signaling axis. A murine model of renal I/R injury was established, and GL-PPQ1 was administered orally for seven days before surgery. The assessment included renal function, histopathology, oxidative stress markers, and inflammatory cytokines. Additionally, transcriptomic profiling and protein expression analyses were conducted to elucidate the underlying mechanisms. The results revealed that GL-PPQ1 pretreatment significantly reduced renal tubular damage, lowered serum creatinine and blood urea nitrogen levels, and diminished oxidative stress and inflammatory responses. RNA sequencing revealed that GL-PPQ1 affected gene sets associated with extracellular matrix remodeling and cell adhesion. Western blot and immunohistochemistry further confirmed that GL-PPQ1 decreased the expression of integrin β3 and Fn1, suggesting a regulatory effect on their interaction during I/R injury. These findings demonstrate that GL-PPQ1 offers substantial kidney protection by mitigating oxidative stress, inflammation, and dysregulation of the integrin β3/Fn1 signaling pathway. Thus, this study supports that polysaccharide peptides derived from Ganoderma lucidum could have the potential to serve as both a dietary supplement and a therapeutic agent in the treatment of AKI.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810393","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":"Antibacterial Mechanism of Dipicolinic Acid Against <i>Xanthomonas citri</i> pv. <i>glycines</i> and Its Efficacy for the Management of Soybean Bacterial Pustule Disease.","authors":"Lei Chen, Jia-Xuan Shen, Ming-Yi Zhang, Xin-Chi Shi, Lei Xu, Si-Yuan Liu, Daniela D Herrera-Balandrano, Pere Clapés, Jie Gong, Dong Liu, Su-Yan Wang, Pedro Laborda","doi":"10.3390/biom16040605","DOIUrl":"10.3390/biom16040605","url":null,"abstract":"<p><p><i>Bacillus</i> species are extensively studied, utilized, and commercialized biocontrol agents, demonstrating significant effectiveness in managing a variety of plant diseases. <i>Bacillus</i> possesses a robust intrinsic biosynthetic ability, capable of producing a diverse array of antimicrobial metabolites, including dipicolinic acid (DPA; 2,6-pyridinedicarboxylic acid), which exhibits antifungal properties and serves as a principal structural component of <i>Bacillus</i> spores. This study revealed that DPA exhibits significant antibacterial activity against the hazardous soybean pathogen <i>Xanthomonas citri</i> pv. <i>glycines</i> (<i>Xcg</i>), with an EC₅₀ value of 53.2 μg/mL. DPA inhibited <i>Xcg</i> swimming motility, extracellular protease activity, and biofilm formation, while inducing significant membrane irregularities in <i>Xcg</i> cells. DPA treatment downregulated the expression of several <i>Xcg</i> membrane integrity-related genes, including <i>cirA</i>, <i>czcA</i>, <i>czcB</i>, <i>emrE</i>, and <i>tolC</i>. The preventive and curative application of 500 μg/mL DPA reduced <i>Xcg</i> symptoms by 82.7% and 83.8%, respectively, and induced the accumulation of the isoflavone genistin in soybean leaves. DPA exhibited only weak toxicity in the zebrafish model, suggesting its potential suitability for agricultural commercialization. Overall, this study provides the first detailed characterization of the antibacterial mechanism of DPA against a phytopathogenic bacterium, <i>Xcg</i>, and identifies DPA as a previously underexplored antibacterial metabolite from <i>Bacillus</i> and <i>Paecilomyces</i> with potential for disease management.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810328","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":"Immunohistochemical Expression of Integrin α_vβ₆ in Surgically Resected Pulmonary Inflammatory Lesions Mimicking Malignancy on ¹⁸F-FDG PET/CT: Implications for the Specificity of ⁶⁸Ga-Trivehexin PET/CT.","authors":"Muin Tuffaha, Amro Tuffaha, Wael Hananeh, Mohammad Khalifeh, Jenny Sonke, Michael Starke","doi":"10.3390/biom16040602","DOIUrl":"10.3390/biom16040602","url":null,"abstract":"<p><p><b>¹⁸</b>F-fluorodeoxyglucose (FDG) PET/CT is widely used for the evaluation of pulmonary lesions but lacks specificity, as increased FDG uptake is frequently observed in inflammatory and reparative processes. This limitation may lead to false-positive interpretations and unnecessary surgical resections. This study aimed to evaluate the immunohistochemical expression of integrin α_vβ₆ in 18 surgically resected pulmonary lesions that were falsely classified as malignant on FDG PET/CT, in order to find out if ⁶⁸Ga-Trivehexin PET/CT could have superior preoperative diagnostic specificity. Histopathological examination classified all lesions as non-neoplastic inflammatory processes of varying etiologies. Integrin α_vβ₆ expression was detected in all immunohistochemically examined tissue specimens (18/18 cases (100%)), with moderate membranous overexpression in 2/18 cases (11.11%) and strong membranous overexpression in 16/18 cases (88.89%) observed in the alveolar and bronchial epithelium of inflammatory lung lesions. Our findings indicate that integrin α_vβ₆ is upregulated not only in neoplastic lung tissue but also in inflammatory lesions, suggesting that integrin α_vβ₆ may have limited specificity for distinguishing primary neoplastic from inflammatory pulmonary lesions when used alone. Its interpretation requires integration with other clinical imaging modalities and histopathological data.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810779","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":"Histone Demethylase JMJD2D Suppresses Influenza A Virus Infection by Promoting RIG-I Expression.","authors":"Xiaochun Xia, Jiadi Liang, Hanshi Guo, Fudong Zhang, Junjie Zhang, Chundong Yu, Pingli Mo, Yilin Hong","doi":"10.3390/biom16040604","DOIUrl":"10.3390/biom16040604","url":null,"abstract":"<p><p>The efficacy of the host antiviral response against Influenza A virus (IAV), a leading cause of global pandemics, hinges upon the rapid recognition of the pathogen and the prompt activation of immune mechanisms. Nevertheless, the epigenetic landscape that orchestrates this antiviral response remains largely elusive. Here, we identify histone demethylase JMJD2D as a critical regulator in defense against IAV infection. A significant upregulation of JMJD2D expression was observed clinically in response to IAV infection, indicating that JMJD2D may play a role in regulating IAV infection. Indeed, JMJD2D-deficient mice exhibit increased susceptibility to IAV, characterized by elevated viral loads, severe lung tissue damage, and reduced survival rates, suggesting that JMJD2D plays an essential role in defense against IAV infection. Consistently, knockdown or pharmacological inhibition of JMJD2D in lung cells suppressed IAV replication and the IAV-triggered innate immune response. Mechanistically, JMJD2D suppressed IAV infection by removing H3K9me3 at the promoter region of retinoic acid inducible gene-I (RIG-I) and cooperating with NF-κB to enhance the expression of RIG-I, a critical sensor for IAV RNA. This study identifies JMJD2D as an epigenetic rheostat that governs RIG-I-mediated antiviral signaling, highlighting its potential as a therapeutic target for mitigating severe IAV infection.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810659","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 Pharmacological Studies on Kynurenic Acid Metabolism in the <i>Helix pomatia</i>-Snail Model of Learning and Memory.","authors":"Halina Baran, Carina Kronsteiner","doi":"10.3390/biom16040603","DOIUrl":"10.3390/biom16040603","url":null,"abstract":"<p><p>Kynurenic acid (KYNA), a metabolite of the L-kynurenine pathway of L-tryptophan degradation, is an endogenous blocker of glutamate ionotropic excitatory amino acid (EAA) receptors and nicotinic acetylcholine receptors (nAChRs). KYNA plays a significant role in various neuropsychiatric disorders and the aging process. Some researchers have suggested that KYNA may contribute to memory impairment. In this study, we examined the impact of L-kynurenine (a KYNA substrate) and the anti-dementia drugs D-cycloserine and Cerebrolysin on kynurenine aminotransferase (KAT) activity, an enzyme forming KYNA, in liver homogenates of <i>Helix pomatia</i> snails. Furthermore, a memory model was established using these snails, wherein tentacle shortening served as an indicator of learning activity. In vitro experiments on <i>Helix pomatia</i> demonstrated the significant impact of L-kynurenine and anti-dementia drugs on KYNA synthesis. KYNA levels increased significantly in the presence of L-kynurenine in liver homogenate. However, KYNA formation decreased when anti-dementia drugs, including Cerebrolysin or D-cycloserine, were administered to the snails' liver homogenate. L-kynurenine has been shown to impair the learning process in vivo in snails, but an anti-dementia drug has been demonstrated to reverse this effect. Significant inhibition of tentacle lowering was observed in response to L-kynurenine treatment, which corresponded with elevated KYNA levels in the central nervous system. Administering D-cycloserine or Cerebrolysin alongside L-kynurenine reversed its effects. The <i>Helix pomatia</i> memory model is a valuable tool for studying learning and memory formation in various conditions and in the presence of different pharmacological agents. A drug or natural extract that blocks KYNA synthesis has the ability to increase tentacle lowering and could be considered an anti-dementia agent. Furthermore, this metabolite may also protect against aging and delay damage to the central nervous system related to memory.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810575","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":"Ghosts on the Membrane: Cytoskeletal Pinning Influences Nanoscale Cell Membrane Organization.","authors":"Shambhavi Pandey, Thorsten Wohland","doi":"10.3390/biom16040596","DOIUrl":"10.3390/biom16040596","url":null,"abstract":"<p><p>The lateral organization of the plasma membrane (PM) is vital for cellular signaling, yet the specific mechanisms by which the internal cortical actin meshwork templates the organization of the external lipid leaflet remain poorly understood. While established models like the 'picket-fence' emphasize physical barriers to diffusion, recent observations of fiber-like \"ghost\" structures in the distribution of glycosylphosphatidylinositol-anchored proteins (GPI-APs) suggest a more intricate mode of spatial coordination. In this study, we utilize imaging total internal reflection fluorescence correlation spectroscopy (ITIR-FCS) and variable-angle TIRF to resolve whether these filamentous patterns represent genuine membrane-proximal features or optical artifacts of cytosolic transport. Our results demonstrate that these fiber-like tracks are strictly confined to the immediate PM interface and disappear as the evanescent field probes deeper into the cytosol. While the spatial distribution of GPI-APs is templated by the underlying actin meshwork, quantitative diffusion mapping shows that the lateral dynamics of the probe remains largely uniform and is not significantly modulated by these filamentous patterns. By pharmacologically perturbing the actin scaffold and membrane cholesterol, we show that this transbilayer coupling is contingent upon a cholesterol-dependent cytoskeletal pinning mechanism. These findings demonstrate a decoupling of spatial organization and molecular dynamics, providing evidence for how the actin scaffold patterns nanoscale membrane organization without imposing long-range barriers to diffusion.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810318","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":"Tau and β-Amyloid Relevant Pathology as a Central Therapeutic Target in Alzheimer's Disease.","authors":"Lidia Strużyńska, Kamil Adamiak, Marta Sidoryk-Węgrzynowicz","doi":"10.3390/biom16040595","DOIUrl":"10.3390/biom16040595","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the leading cause of dementia, responsible for approximately 60-70% of cases globally. AD is a gradually progressive neurodegenerative disorder that is characterized by widespread deposition of β-amyloid (Aβ) plaques, followed by aggregation of tau protein in the neocortex, neurodegeneration, and cognitive decline. Within these complex pathological interactions, Aβ and tau proteins, together with astrogliosis, neuroinflammation, and other factors, play a key role in the development of clinical AD. Accumulating evidence indicates that the formation of protein oligomers, followed by their aggregation into pathological fibrils, constitutes an early and critical step in the pathogenesis of the disease. Specific pathological proteins are often treated as biomarkers of particular diseases because their presence, concentration, or altered structure reflects an underlying disease process. It is well established that the Aβ and tau proteins are the key hallmarks of AD, and their mutual interaction may significantly influence the pathology of the disease. Early diagnosis is crucial for maximizing the therapeutic benefits of currently available symptomatic treatments, which can alleviate symptoms and modestly delay clinical deterioration in patients with AD. This review highlights the mechanisms involved in protein-dependent neurodegeneration and describes both traditional and novel approaches for the cure of AD. The most important aspect of this publication is the integration of the two key proteins: Aβ and tau, and the resulting shift toward a new therapeutic approach.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810761","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":"Emerging Role of Transcription Factor 19 (TCF19) in Inflammatory Disease and Cancer.","authors":"Xiang Li, Yi-Fang Jiang, Ran Wang, Jing Yu, Yan-Jun Liu, Yun-Fei Dang, Guan-Jun Yang, Jiong Chen","doi":"10.3390/biom16040600","DOIUrl":"10.3390/biom16040600","url":null,"abstract":"<p><p>Transcription factor 19 (TCF19) is a multifunctional biomolecule located within the major histocompatibility complex (MHC) class I region on chromosome 6p21.3. Structurally, TCF19 contains a plant homeodomain (PHD) finger that recognizes histone H3 lysine 4 trimethylation (H3K4me3) and a forkhead-associated (FHA) domain with yet-uncharacterized functions. Emerging evidence positions TCF19 as a multifunctional regulator associated with cell cycle progression, transcriptional regulation, cancer progression, and immune modulation through epigenetic and signaling mechanisms. This review provides the first systematic synthesis of TCF19's structural domains, regulatory networks, and context-dependent functions across cancer and non-cancer diseases. We highlight critical knowledge gaps, including the unresolved function of its FHA domain and the lack of direct small-molecule inhibitors. In cancer, TCF19 drives proliferation, metastasis, immune evasion, and therapy resistance. Beyond cancer, TCF19 is involved in metabolic diseases, chronic infections, inflammatory disorders, and sensory deficits. TCF19 serves as a promising molecular biomarker for cancer diagnosis, prognosis, and treatment response monitoring, though direct targeting strategies remain unavailable.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810953","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":"A Highly Conserved Glycine in a Hotspot for Neurological Disease Mutations in Na⁺,K⁺-ATPase Is Critical to Na⁺ and K⁺ Occlusion.","authors":"Mads S Toustrup-Jensen, Rikke Holm, Jens Peter Andersen, Bente Vilsen","doi":"10.3390/biom16040601","DOIUrl":"10.3390/biom16040601","url":null,"abstract":"<p><p>Na⁺,K⁺-ATPase possesses a highly conserved glycine (G358 in the α3 isoform) that-together with a nearby isoleucine (I363 in α3)-is targeted by mutations causing some of the most severe neurological phenotypes of the clinical spectrum of α3-Na⁺,K⁺-ATPase mutations. The disease mutations α3-G358V and α3-I363N affect Na⁺ and K⁺ transport to an extent incompatible with cell growth. However, alanine replacement of the corresponding glycine G363 in the α1 isoform is compatible with cell growth, allowing the effects on Na⁺,K⁺-ATPase function to be addressed using enzymatic assays on plasma membranes isolated from transfected cells. Occlusion of Na⁺ appears to be defective in mutant G363A, resulting in a reduced rate of phosphorylation from ATP. Furthermore, the mutation displaces the major conformational equilibrium of Na⁺,K⁺-ATPase such that the K⁺-occluded state is destabilized and occluded K⁺ is released faster, thereby leading to accumulation of a non-productive state without bound Na⁺ or K⁺. The critical function of the glycine can be ascribed to a strategic location at the bending point between an α helix and a β strand, where it connects the catalytic ATP hydrolysis site in the cytoplasmic P domain with the ion-binding region in the membrane and coordinates important intramolecular domain movements during the Na⁺,K⁺-ATPase transport cycle.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810776","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":"Fragment-Derived Nicotinic Acid Analogues Inhibit hCA III and Downregulate <i>CA3</i> Expression in HepG2 Cells.","authors":"Areej Abuhammad, Tamara Sabri, Nidaa A Ababneh, Rya A Ali, Mohammad A Ismail, Adan Madadha, Dareen T Yazjeen, Rama J Alghanem, Ali M Qaisi, Yusuf Al-Hiari, Kapil Gupta, Imre Berger, Edith Sim","doi":"10.3390/biom16040599","DOIUrl":"10.3390/biom16040599","url":null,"abstract":"<p><p>Chronic oxidative stress and lipid imbalance drive metabolic disorders such as obesity and non-alcoholic fatty liver disease, yet few therapies target the upstream redox imbalance in key tissues. Human carbonic anhydrase III (hCA III), a redox-associated enzyme enriched in liver and adipose tissue, has long remained pharmacologically elusive due to its low catalytic activity and lack of modulators. Here, we identify fragment-like nicotinic acid derivatives as non-sulfonamide hCA III modulators and evaluate their associated cellular effects. Using an esterase activity assay, we screened 25 analogues and identified two fragment-like hits, compound <b>17</b> (2-thioethyl) and compound <b>22</b> (6-morpholino), with IC₅₀ values of 487 and 361 µM, respectively. Orthogonal thermal shift analysis supported compound-protein interaction, and selected hits were subsequently evaluated in HepG2 cells. Both compounds were associated with reduced <i>CA3</i> mRNA expression after treatment at 1 µM, while their cellular phenotypes diverged, with compound <b>22</b> increasing ROS under oxidative stress conditions and compound <b>17</b> affecting mitochondrial membrane potential. Taken together, these findings identify tractable nicotinic acid-derived fragment hits and associated cellular phenotypes that warrant further mechanistic investigation. These fragment-like hits provide a practical starting point for studying the redox-linked biology of hCA III.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 4","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13113631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810325","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}