Clinical science最新文献

{"title":"Early detection and progression of insulin resistance revealed by impaired organismal anti-inflammatory heat shock response during ex vivo whole-blood heat challenge.","authors":"Helena Trevisan Schroeder, Carlos Henrique de Lemos Muller, Maria Inês Lavina Rodrigues, Marcela Alves de Azevedo, Thiago Gomes Heck, Mauricio Krause, Paulo Ivo Homem de Bittencourt","doi":"10.1042/CS20243515","DOIUrl":"10.1042/CS20243515","url":null,"abstract":"<p><p>Chronic inflammatory diseases, e.g., obesity, cardiovascular disease and type-2 diabetes, progressively suppress the anti-inflammatory heat shock response (HSR) by impairing the synthesis of key components, perpetuating inflammation. Monitoring HSR progression offers predictive value for countering chronic inflammation. This study quantified HSR in high-fat diet (HFD) and normal chow (NC) mice by measuring 70 kDa heat shock protein (HSP70) expression after heat treatment of whole blood samples. To align with human translational relevance, animals were housed within their thermoneutral zone (TNZ). Whole blood was heat-challenged weekly at 42 °C for 1-2 hours over 22 weeks, and ΔHSP70 was calculated as the difference between HSP70 expressions at 42 °C and 37 °C. Results correlated with fasting glycaemia, oral glucose tolerance test, intraperitoneal insulin tolerance test and 2-hour post-glucose load glycaemia. ΔHSP70 levels >0.2250 indicated normal fasting glycaemia, while levels <0.2125 signalled insulin resistance and type-2 diabetes onset. A logistic model (five-parameter logistic) showed progressive HSR decline, with HFD mice exhibiting earlier ΔHSP70 reduction (t1/2 = 3.14 weeks) compared with NC mice (t1/2 = 8.24 weeks), highlighting compromised anti-inflammatory capacity in both groups of mice maintained at TNZ. Remarkably, even NC mice surpassed insulin resistance thresholds by week 22, relevant as control diets confronted interventions. Observed HSR decline mirrors tissue-level suppression in obese and type-2 diabetic individuals, underscoring HSR failure as a hallmark of obesity-driven inflammation. This study introduces a practical whole-blood assay to evaluate HSR suppression, allowing assessment of glycaemic status during obesity onset before any clinical manifestation.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"85-113"},"PeriodicalIF":6.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging and sex differences in salt sensitivity of blood pressure.","authors":"Mert Demirci, Jeremiah M Afolabi, Annet Kirabo","doi":"10.1042/CS20240788","DOIUrl":"10.1042/CS20240788","url":null,"abstract":"<p><p>Salt sensitivity of blood pressure (SSBP) is a complex physiological trait characterized by changes in blood pressure in response to dietary salt intake. Aging introduces an additional layer of complexity to the pathophysiology of SSBP, with mitochondrial dysfunction, epigenetic modifications, and alterations in gut microbiota emerging as critical factors. Despite advancements in understanding these mechanisms, the processes driving increased salt sensitivity with age and their differential impacts across sexes remain unclear. This review explores the current understanding of salt sensitivity, delving into its underlying mechanisms, the role of inflammation, and the influence of aging and sex differences on these processes. We also aim to provide insights into the multifaceted nature of salt sensitivity and its implications for personalized treatment strategies in hypertension management.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"139 2","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heme oxygenase, biliverdin reductase, and bilirubin pathways regulate oxidative stress and insulin resistance: a focus on diabetes and therapeutics.","authors":"Wang-Hsin Lee, Zachary A Kipp, Sally N Pauss, Genesee J Martinez, Evelyn A Bates, Olufunto O Badmus, David E Stec, Terry D Hinds","doi":"10.1042/CS20242825","DOIUrl":"10.1042/CS20242825","url":null,"abstract":"<p><p>Metabolic and insulin-resistant diseases, such as type 2 diabetes mellitus (T2DM), have become major health issues worldwide. The prevalence of insulin resistance in the general population ranges from 15.5% to 44.6%. Shockingly, the global T2DM population is anticipated to double by 2050 compared with 2021. Prior studies indicate that oxidative stress and inflammation are instrumental in causing insulin resistance and instigating metabolic diseases. Numerous methods and drugs have been designed to combat insulin resistance, including metformin, thiazolidinediones (TZDs), sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide 1 receptor agonists (GLP1RA), and dipeptidyl peptidase 4 inhibitors (DPP4i). Bilirubin is an antioxidant with fat-burning actions by binding to the PPARα nuclear receptor transcription factor, improving insulin sensitivity, reducing inflammation, and reversing metabolic dysfunction. Potential treatment with antioxidants like bilirubin and increasing the enzyme that produces it, heme oxygenase (HMOX), has also gained attention. This review discusses the relationships between bilirubin, HMOX, and insulin sensitivity, how T2DM medications affect HMOX levels and activity, and potentially using bilirubin nanoparticles to treat insulin resistance. We explore the sex differences between these treatments in the HMOX system and how bilirubin levels are affected. We discuss the emerging concept that bilirubin bioconversion to urobilin may have a role in metabolic diseases. This comprehensive review summarizes our understanding of bilirubin functioning as a hormone, discusses the HMOX isoforms and their beneficial mechanisms, analyzes the sex differences that might cause a dichotomy in responses, and examines the potential use of HMOX and bilirubin nanoparticle therapies in treating metabolic diseases.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"139 2","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-mediated effects of transglutaminase 2 inhibition on endothelial function in human resistance arteries from diabetic and non-diabetic patients.","authors":"Khatera Saii, Judit Prat-Duran, Ulf Simonsen, Anders Riegels Knudsen, Jonas Amstrup Funder, Niels Henrik Buus, Estéfano Pinilla","doi":"10.1042/CS20242001","DOIUrl":"10.1042/CS20242001","url":null,"abstract":"<p><p>Transglutaminase 2 (TG2) is an enzyme with multiple conformations. In its open conformation, TG2 exhibits transamidase activity linked to fibrosis, arterial remodeling, and endothelial dysfunction, a process enhanced by high glucose in endothelial cells. However, the closed conformation of TG2 contributes to transmembrane signaling and nitric oxide (NO)-dependent vasorelaxation. LDN 27219, a reversible allosteric inhibitor, stabilizes TG2 in its closed conformation. We examined whether pharmacological modulation of TG2 into its closed conformation induces vasorelaxation and enhances endothelium-dependent and independent relaxation in resistance arteries from age-matched diabetic (n = 14) and non-diabetic patients (n = 14) (age 71 (Standard Error of the Mean: ± 2)). Subcutaneous arteries (diameter 133-1013 µm) were isolated from abdominal fat biopsies. TG2 mRNA expression and transamidase activity were assessed via RT-qPCR and 5-biotin(amido)pentylamine (5-BP) incorporation, while vascular reactivity was measured using wire myography. TG2 mRNA was highly expressed without significant differences between the groups and LDN 27219 induced concentration-dependent vasorelaxation in arteries from both groups. Sex-specific analysis revealed that potentiation of acetylcholine-induced vasorelaxation by LDN 27219 was driven by increased TG2 expression in non-diabetic females, whereas no effect was observed in arteries from non-diabetic males. Among diabetic patients, LDN 27219 increased maximal acetylcholine-induced vasorelaxation in males only. LDN 27219 did not affect endothelium-independent relaxation to sodium nitroprusside in either group. In conclusion, TG2 is expressed in human resistance arteries, and LDN 27219 induced vasorelaxation, selectively enhancing ACh relaxation in non-diabetic females, likely owing to increased TG2 expression. This finding underscores the importance of sex differences in TG2 modulation of vasorelaxation.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"1-14"},"PeriodicalIF":6.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct effects of obesity and diabetes on the action potential waveform and inward currents in rat ventricular myocytes.","authors":"Anatoliy Shmygol, Gilles Bru-Mercier, Ahmed S Sultan, Frank C Howarth","doi":"10.1042/CS20242144","DOIUrl":"10.1042/CS20242144","url":null,"abstract":"<p><p>Obesity is a significant global health challenge, increasing the risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular disease. Research indicates that obese individuals, regardless of their diabetic status, have an increased risk of cardiovascular complications. Studies suggest that these patients experience impaired electrical conduction in the heart, although the underlying cause-whether due to obesity-induced fat toxicity or diabetes-related factors-remains uncertain. This study investigated ventricular action potential parameters, as well as sodium (INa) and calcium (ICa, L) currents, in Zucker fatty (ZF) rats and Zucker diabetic fatty (ZDF) rats, which serve as models for obesity and T2DM, respectively. Ventricular myocytes were isolated from 25- to 30-week-old Zucker rats. Resting and action potentials were recorded using a β-escin perforated patch clamp, while INa and ICa,L were assessed with whole-cell patch clamp methods. ZF rats exhibited higher excitability and faster upstroke velocity with greater INa density, whereas ZDF rats showed decreased INa and slower action potential upstroke. No differences in ICa,L density or voltage sensitivity were found among the groups. In summary, obesity, with or without accompanying T2DM, distinctly impacts the action potential waveform, INa density, and excitability of ventricular myocytes in this rat model of T2DM.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"55-67"},"PeriodicalIF":6.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arterial effects of anthracycline: structural and inflammatory assessments in non-human primates and lymphoma patients.","authors":"Stephen Rankin, Caitlin Fountain, Alastair J Gemmell, Daire Quinn, Alasdair Henderson, John McClure, Sandy Small, Balaji Venugopal, Pamela McKay, Piotr J Slomka, David Colville, Mark C Petrie, Giselle C Meléndez, Ninian N Lang","doi":"10.1042/CS20241529","DOIUrl":"10.1042/CS20241529","url":null,"abstract":"<p><p>Anthracyclines, such as doxorubicin, are important anti-cancer therapies but are associated with arterial injury. Histopathological insights have been limited to small animal models, and the role of inflammation in the arterial toxic effects of anthracycline is unclear in humans. Our aims were (1) to evaluate aortic media fibrosis and injury in non-human primates treated with anthracyclines; (2) to assess the effect of anthracycline on aortic inflammation in patients treated for lymphoma. African Green monkeys (AGMs) received doxorubicin (30-60 mg/m2/biweekly intravenously, cumulative dose: 240 mg/m2). Blinded histopathologic analyses of the ascending aorta were performed 15 weeks after the last doxorubicin dose and compared to five age- and gender-matched healthy, untreated AGMs. Analysis of the thoracic aorta of patients with diffuse large B-cell lymphoma (DLBCL), at baseline and after doxorubicin exposure, was performed using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in this observational study by maximal tissue-to-background ratio (TBRmax). In AGMs, doxorubicin exposure was associated with greater aortic fibrosis (collagen deposition: doxorubicin 6.23 ± 0.88% vs. controls 4.67 ± 0.54%; P=0.01) and intracellular vacuolization (doxorubicin 66.3 ± 10.1 vs. controls 11.5 ± 4.2 vacuoles/field, P<0.0001) than untreated controls. In 101 patients with DLBCL, there was no change in aortic TBRmax after anthracycline exposure (TBRmax 1.46 ± 0.16 vs. 1.44 ± 0.14, respectively, P=0.14). Univariate analyses yielded similar results. In a large animal model, anthracycline exposure was associated with aortic fibrosis. In patients with lymphoma, anthracycline exposure was not associated with aortic inflammation. Further research is required to elucidate the mechanisms of anthracycline-related vascular harm.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"29-41"},"PeriodicalIF":6.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA-binding protein HuR regulates the transition of septic AKI to CKD by modulating CD147.","authors":"Simeng Liu, Renfei Luo, Davey Li, Anna Tang, Yuli Qiu, Ryan P Sherrier, Jeffrey Aube, Xiaoqing Wu, Liang Xu, Yufeng Huang","doi":"10.1042/CS20241756","DOIUrl":"10.1042/CS20241756","url":null,"abstract":"<p><p>Septic acute kidney injury (AKI) is an important risk factor for developing chronic kidney disease (CKD). Hu antigen R (HuR) is recognized as a crucial modulator in inflammation. We hypothesized that elevated HuR contributes to the transition from septic AKI to CKD by promoting persistent inflammation and fibrosis, and inhibition of HuR may reverse septic kidney injury. Mice subjected to lipopolysaccharide (LPS) injections every other day were concurrently treated without or with either KH39 or niclosamide (NCS) for 7 days. Control mice received saline injections. Repeated LPS injections led to a significant increase in HuR expression in the kidneys, which was effectively suppressed by KH39 or NCS treatment. LPS-induced kidney injury was characterized by elevated plasma blood urea nitrogen levels and urinary albuminuria, along with histological signs of inflammatory cell infiltration and fibrosis, as determined by periodic acid-Schiff and Masson's trichrome staining, and immunofluorescent staining for markers such as α-smooth muscle actin, fibronectin, collagen III, and F4/80. Treatment with either KH39 or NCS mitigated these changes observed in LPS-injured kidneys. Additionally, increased expression of CD147, a molecule implicated in inflammatory cell recruitment and tubular injury, was inhibited by KH39 or NCS treatment. These effects on HuR and CD147 expression were further validated in vitro in cultured macrophages and tubular cells. This study suggests that HuR elevation in LPS-stimulated macrophages and kidney cells contributes to the progression of septic kidney injury, possibly through HuR-CD147 interactions, underscoring the therapeutic potential of HuR inhibitors for this condition.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"69-84"},"PeriodicalIF":6.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SMAD5 as a novel gene for familial pulmonary arterial hypertension.","authors":"Ding Cao, Ekkehard Grünig, Yuriy Sirenko, Ganna Radchenko, Henning Gall, Ayat Ahmed, Susanne Theiß, Mareike Lankeit, Benjamin Meder, Magdalena Laugsch, Christina A Eichstaedt","doi":"10.1042/CS20241340","DOIUrl":"10.1042/CS20241340","url":null,"abstract":"<p><p>Genetic diagnostic testing of 325 pulmonary arterial hypertension (PAH) patients using a PAH specific gene panel including 18 known PAH genes revealed mutations in 23%. Further PAH candidate genes were sequenced in the remaining patients exposing two SMAD5 variants, which were clinically and functionally characterized. We first recorded familial cosegregation and clinical parameters. Functional tests were performed following transient over-expression of the two SMAD5 variants in pulmonary artery smooth muscle cells (PASMCs). Expression of these variants was confirmed by quantitative PCR, Sanger sequencing, and Western blotting. Cell viability was evaluated using cell counting kit 8, cell proliferation by bromodeoxyuridine (BrdU), and apoptosis by annexin V assay. Both SMAD5 missense variants were absent in healthy controls and predicted to be pathogenic. The variant c.1175T>C p.(Leu392Pro) was identified in a heritable PAH patient and her healthy son. The mother had died of suspected PAH at age 42. The expression of this variant in PASMCs led to significantly higher cell viability due to higher proliferation in comparison with SMAD5 wild-type cells. The second variant c.277T>A p.(Trp93Arg) was identified in a patient with congenital heart disease associated PAH with a surgically repaired ventricular septal defect. Its expression led to significantly lower cell viability due to increased apoptosis in comparison with wild-type SMAD5 cells. Taking into account familial aggregation, clinical findings, and functional evidence, both variants could be classified as likely pathogenic. This is the first description of SMAD5 as a potential novel PAH gene for genetic diagnostic testing.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"15-27"},"PeriodicalIF":6.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Higher circulating ACE2 and DPP3 but reduced ACE and angiotensinogen in hyperreninemic sepsis patients.","authors":"Mark C Chappell, Christopher L Schaich, Laurence W Busse, D Clark Files, Greg S Martin, Jonathan E Sevransky, Jeremiah S Hinson, Richard E Rothman, Ashish K Khanna","doi":"10.1042/CS20242168","DOIUrl":"10.1042/CS20242168","url":null,"abstract":"<p><p>Sepsis and septic shock are global healthcare problems associated with high mortality rates. Activation of the renin-angiotensin-aldosterone system (RAAS) is an early event in sepsis, and elevated renin may be predictive of worse outcomes. In a subset of sepsis patients enrolled in the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial, elevated levels of active renin (median value > 189 pg/mL or 5.1 pM) at baseline (day 0) were strongly associated with mortality; however, corresponding plasma levels of the vasopressor hormone Angiotensin II were not substantially increased nor was Angiotensin II associated with disease severity. The current study assessed RAAS components that may impact the Angiotensin II response in control subjects, normal renin sepsis (NRS, renin < 5.1 pM) and high renin sepsis (HRS, renin > 5.1 pM) patients. NRS and HRS subjects exhibited a similar reduction in ACE (40%), but increased levels of ACE2 and DPP3. The ACE to DPP3 ratio was higher in controls but this relationship was reversed in both NRS and HRS subjects. Intact angiotensinogen was 50% lower in the HRS than control or NRS subjects, whereas the intact angiotensinogen to renin ratio was <10% of control or NRS subjects. We conclude that altered expression of ACE, ACE2, DPP3 and angiotensinogen may attenuate the expected increase in Angiotensin II, particularly in sepsis subjects with high renin concentrations.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":" ","pages":"43-53"},"PeriodicalIF":6.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12053747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insight into the roles of lactylation in macrophages: functions and clinical implications.","authors":"Min Shu, Dingci Lu, Ziyi Zhu, Fei Yang, Zhaowu Ma","doi":"10.1042/CS20242737","DOIUrl":"10.1042/CS20242737","url":null,"abstract":"<p><p>Lactylation, a post-translational modification, has been linked to gene transcription regulation through epigenetic modulation in various pathophysiological processes. The lactylation regulatory proteins, known as writers, erasers, and readers, govern their dynamics by adding, removing, and recognizing lactyl groups on proteins. Macrophages, as cells of the immune system, maintain homeostasis, responding dynamically to diverse internal and external stimuli. Emerging researches unveil that lactylation, through inducing macrophage activation and polarization, affects their functionality in pathological conditions such as inflammation, tumor microenvironment, and fibrosis. Evidence progressively indicates that lactate-driven alterations in lactylation levels within macrophages can influence the pathogenesis of numerous diseases. This review aims to systematically summarize the research progress of lactylation in macrophages, explore its functions and mechanisms by which lactylation contributes to the pathology of different disease phenotypes, and propose future research directions along with potential diagnostic and therapeutic strategies.</p>","PeriodicalId":10475,"journal":{"name":"Clinical science","volume":"139 2","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12204002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}