Histology and histopathology最新文献

{"title":"PAQR11: An evolutionarily conserved Golgi receptor governing metabolic-immune crosstalk and systemic homeostasis.","authors":"Yu-Zhen Zhang, Pei Li, Zhi Qiang Ling","doi":"10.14670/HH-25-080","DOIUrl":"10.14670/HH-25-080","url":null,"abstract":"<p><p>PAQR11, an evolutionarily conserved seven-transmembrane receptor localized at the Golgi apparatus, functions as a master coordinator of metabolic-immune integration across physiological systems. This review synthesizes cutting-edge evidence revealing how its unique subcellular positioning enables compartmentalized regulation of Ras signaling and inflammasome activation through allosteric conformational switching, thereby governing immunometabolic adaptations from <i>Caenorhabditis elegans</i> to mammals. Pathophysiologically, PAQR11 disruption precipitates multisystem disorders: impaired insulin sensitivity and adipokine signaling exacerbate obesity-associated lipotoxicity; enhanced NLRP3 activation via Ras scaffolding drives autoimmune pathogenesis; and rewired fatty acid oxidation coordinates tumor-stromal crosstalk in obesity-related malignancies. Mechanistically, PAQR11 operates as a spatiotemporal organizer by assembling signaling hubs at the Golgi membrane-its 7TM domain acting as a ligand-gated switch for signal bias-while emerging roles in circadian immunometabolism highlight broader implications for systemic homeostasis. Future research must resolve tissue-specific receptor interactomes and exploit cross-species conservation for targeted physiological modulation, bridging molecular architecture with organismal pathophysiology.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1791-1798"},"PeriodicalIF":2.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alginate gel embedding preserves antigenicity in free-floating brain sections.","authors":"Mihaela Abuzan, Andreea Cercel, Dirk M Hermann, Razvan Capitanescu, Aurel Popa-Wagner","doi":"10.14670/HH-25-075","DOIUrl":"10.14670/HH-25-075","url":null,"abstract":"<p><p>Free-floating cryosections are widely used in neuroanatomical and immunohistochemical studies due to their superior antigen preservation and unrestricted antibody penetration. However, long-term storage of these sections is vulnerable to freezer failures, often resulting in irreversible loss of irreplaceable material. To address this limitation, we developed an alginate gel embedding method designed to protect free-floating brain sections after cryotome cutting and maintain antigenicity during extended storage at -40°C. Using a mouse model of ischemic stroke, we evaluated antigen stability under simulated freezer accident conditions by analyzing immunofluorescence for CD68, GFAP, Iba1, and NeuN in consecutive sections exposed to room temperature for 0, 1, or 2 days. CD68 and Iba1 signals showed partial decline by day 2, whereas GFAP and NeuN immunoreactivity remained largely preserved, with only minor reductions in intensity. These results demonstrate that antigen stability varies across markers but can be substantially maintained when sections are embedded in alginate gel. Our findings highlight a simple and effective strategy for long-term preservation of free-floating cryosections and support its use as a safeguard against tissue degradation during storage interruptions. This method offers a practical solution for laboratories relying on extended experimental timelines and repeated immunohistochemical analyses.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1815-1820"},"PeriodicalIF":2.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms involved in eyelid ptosis surgery by conjunctivomüllerectomy: a histopathological and clinical study.","authors":"Andrés Jesús Peñalver-Alcaraz, María Dolores Romero-Caballero, Cristina Godoy-Alba, Ana María Gómez-Ramírez","doi":"10.14670/HH-25-157","DOIUrl":"https://doi.org/10.14670/HH-25-157","url":null,"abstract":"<p><strong>Background: </strong>Conjunctivomüllerectomy is a well-established posterior approach for the surgical treatment of mild-to-moderate aponeurotic blepharoptosis with a positive 2.5% phenylephrine test, but the mechanisms by which it achieves adequate eyelid elevation remain incompletely understood. The aim of this study was to quantify the proportion of Müller's muscle present in surgical specimens, to evaluate the degree of chronic inflammation in the resected tissue, and to correlate these histological findings with postoperative clinical outcomes assessed by margin reflex distance 1 (MRD1).</p><p><strong>Materials and methods: </strong>A prospective, observational clinical study was conducted on fifteen eyes from fourteen consecutive patients (mean age 68.9±11.7 years) with aponeurotic blepharoptosis, preserved levator function and a positive 2.5% phenylephrine test, who underwent conjunctivomüllerectomy according to the modified Putterman technique. Surgical specimens were processed for histological and immunohistochemical analysis. The percentage of Müller's muscle was quantified using smooth muscle actin, desmin and h-caldesmon, and chronic inflammation was assessed by the maximum number of plasma cells per high-power field (CD138 and CD38). MRD1 was measured before and four weeks after surgery.</p><p><strong>Results: </strong>No Müller's muscle was identified in 33% of the specimens, while the mean proportion in the remaining samples was 29.7 ± 31.5%. Levator aponeurosis and skeletal muscle fibres were absent in all cases. Chronic inflammation was present in 87% of specimens. Mean MRD1 improved from 1.05 ± 0.58 mm preoperatively to 3.77±0.46 mm postoperatively (<i>p</i><0.001). MRD1 improvement showed a weak negative correlation with the percentage of Müller's muscle and a weak positive correlation with the number of plasma cells per high-power field.</p><p><strong>Conclusions: </strong>The amount of Müller's muscle resected does not appear to be the main determinant of clinical success after conjunctivomüllerectomy. Chronic conjunctival inflammation may play a role in postoperative eyelid elevation through wound contraction and posterior lamella shortening. Conjunctivomüllerectomy is an effective technique for aponeurotic blepharoptosis, with greater benefit in older patients and in milder degrees of ptosis.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25157"},"PeriodicalIF":2.2,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanism of total flavonoids of hawthorn leaves in spinal cord injury treatment: A combined network pharmacology and experimental study.","authors":"Ting Zhu, Wenwen Fu, Yiguang Bai, Rufei Wei, Jieqiong Huang, Gaofeng Zeng","doi":"10.14670/HH-25-156","DOIUrl":"https://doi.org/10.14670/HH-25-156","url":null,"abstract":"<p><strong>Background and objective: </strong>Spinal cord injury (SCI) is a devastating neurological disorder characterized by irreversible motor and sensory dysfunction, largely driven by secondary injury mechanisms including oxidative stress, inflammation, and apoptosis. Total flavonoids of hawthorn leaves (TFHL), a traditional Chinese medicine, have demonstrated antioxidant and anti-inflammatory properties; however, their therapeutic effects and mechanisms in SCI remain unclear.</p><p><strong>Methods: </strong>Network pharmacology was employed to identify the active compounds, potential targets, and key signaling pathways of TFHL in SCI through target prediction, protein-protein interaction analysis, and GO and KEGG enrichment analyses. Experimental validation was performed using a rat SCI model, LPS-stimulated BV-2 microglial cells, and RAW264.7 macrophages. Functional recovery was assessed by BBB scoring, while histopathological changes, ultrastructural alterations, inflammatory cytokine expression, and MAPK pathway activation were evaluated using H&amp;E staining, transmission electron microscopy, RT-qPCR, and western blotting.</p><p><strong>Results: </strong>Network pharmacology analysis identified 15 active compounds and 69 overlapping therapeutic targets, mainly enriched in pathways related to inflammation, oxidative stress, apoptosis, and neuronal survival, including MAPK, PI3K-Akt, TNF, and NF-kB signaling pathways. <i>In vivo</i>, TFHL treatment significantly improved locomotor recovery, alleviated histological damage, preserved mitochondrial structure, and reduced the expression of pro-inflammatory cytokines following SCI. In vitro, TFHL markedly suppressed LPS-induced activation of the MAPK pathway in microglial cells.</p><p><strong>Conclusion: </strong>TFHL improves functional and histopathological outcomes in SCI models and attenuates inflammatory activation. These effects are consistent with multi-pathway regulation predicted by network pharmacology and are supported, at least in part, by MAPK pathway suppression, warranting further mechanistic and translational studies.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25156"},"PeriodicalIF":2.2,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DHA as a systems regulator of neuroinflammation: A narrative review integrating membrane organization, immunometabolism, and inflammatory resolution.","authors":"Marcia Barbosa Aguila, Carlos Alberto Mandarim-de-Lacerda","doi":"10.14670/HH-25-155","DOIUrl":"https://doi.org/10.14670/HH-25-155","url":null,"abstract":"<p><p>Neuroinflammation is a central feature of brain aging and a major driver of neurodegenerative and neuropsychiatric disorders. Conventional anti-inflammatory strategies have produced inconsistent clinical outcomes, reflecting the biological complexity of chronic neuroinflammation and the limited capacity of single-target interventions to modulate interconnected pathogenic pathways. This narrative review synthesizes evidence from mechanistic studies, clinical trials, and meta-analyses identified through structured searches of PubMed, Scopus, and Web of Science. Docosahexaenoic acid (DHA), the predominant omega-3 fatty acid in the brain, modulates neuroinflammatory processes through coordinated effects on membrane organization, intracellular signaling, mitochondrial function, and inflammatory resolution. DHA remodeling of membrane phospholipids alters lipid raft-dependent signaling, attenuates activation of nuclear factor kappa B (NF-κB) and the NLR family pyrin domain-containing 3 (NLRP3) inflammasome, enhances mitochondrial bioenergetics and redox homeostasis, and promotes the generation of specialized pro-resolving mediators. Aging-associated processes, including microglial priming, metabolic dysfunction, impaired lipid transport, blood-brain barrier (BBB) dysfunction, and altered glial responsiveness, further reshape DHA availability and therapeutic responsiveness. These factors contribute to heterogeneous clinical outcomes, as intervention studies often fail to account for baseline omega-3 status, genetic variability, metabolic phenotype, formulation-dependent bioavailability, disease stage, and exposure duration. Emerging lipidomic and biomarker-guided approaches may better characterize biological heterogeneity in DHA intervention studies. We propose a systems-level model in which DHA integrates structural, bioenergetic, and immune-resolution domains governing neuroinflammatory homeostasis, adaptive resilience, and vulnerability to neurodegeneration during aging.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25155"},"PeriodicalIF":2.2,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histopathologic features and subtypes of invasive cutaneous squamous cell carcinoma: A comprehensive review.","authors":"Gerardo Cazzato, Kim Harnisch, Antonina Kalmykova, Phillip McKee","doi":"10.14670/HH-25-154","DOIUrl":"https://doi.org/10.14670/HH-25-154","url":null,"abstract":"<p><p>Invasive cutaneous squamous cell carcinoma (cSCC) is the second most common cutaneous malignancy after basal cell carcinoma and displays a remarkably heterogeneous spectrum of histopathologic variants, several of which pose significant diagnostic challenges and carry distinct clinical, immunohisto-chemical, and molecular implications. In this review, we discuss the principal histopathologic subtypes of invasive cSCC, including acantholytic, sarcomatoid (carcinosarcoma/metaplastic), spindle cell, clear cell, verrucous, papillary, pigmented, adenosquamous, signet ring cell, rhabdoid, lymphoepithelial, and squamo-melanocytic variants, as well as cSCC associated with Merkel cell carcinoma and tumors showing single-cell infiltration. For each entity, we summarize the characteristic clinical presentation, key histopathological features, differential diagnosis, immunohistochemical profile, and, where available, molecular alterations, with particular attention to UV-induced mutations in TP53, NOTCH1/2, and CDKN2A shared across most subtypes. Treatment and prognostic data are also reviewed, highlighting that while most variants follow conventional surgical principles for cSCC, with margin-controlled excision and Mohs micrographic surgery playing a central role, certain subtypes-namely spindle cell/sarcomatoid, rhabdoid, and tumors with single-cell infiltration-are associated with markedly more aggressive behavior and require intensified management. Conversely, entities such as acantholytic, clear cell, verrucous, papillary, and pigmented SCC generally behave indolently despite sometimes alarming histological appearances. Overall, prognosis in cSCC remains primarily driven by established risk factors-tumor size, depth, differentiation, location, and perineural invasion-rather than histologic subtype alone. A refined understanding of these variants, supported by targeted immunohistochemistry and molecular evaluation when indicated, is essential for accurate diagnosis, appropriate risk stratification, and optimal treatment planning.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25154"},"PeriodicalIF":2.2,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peroxiredoxin 4 expression in rapidly destructive coxarthrosis potentially serves as a candidate tissue-level indicator associated with the local antioxidant status.","authors":"Dung Anh Vu, Yao Liu, Thao Thanh Nguyen, Jia Han, Yukinobu Ito, Takeru Oyama, Miyako Shimasaki, Ayumi Kaneuji, Toru Ichiseki, Sohsuke Yamada","doi":"10.14670/HH-25-153","DOIUrl":"https://doi.org/10.14670/HH-25-153","url":null,"abstract":"<p><p>Rapidly destructive coxarthrosis (RDC) is a clinically challenging progressive hip disorder characterized by severe and accelerated joint destruction; however, the local antioxidant response in RDC remains unclear. In steroid-associated osteonecrosis of the femoral head, peroxiredoxin 4 (PRDX4) has recently been suggested to be retained in relatively preserved tissue areas but reduced in association with oxidative injury. Given its established roles in antioxidant defense and tissue protection under oxidative stress, PRDX4 was considered a plausible marker for assessing the local redox response in RDC. This study examined the clinicopathological significance of PRDX4 and its relationship with oxidative damage in femoral head lesions from patients with RDC mainly using histopathology and immunohistochemistry. Femoral head specimens from patients with RDC undergoing hip replacement were compared to those from primary osteoarthritis (POA) controls. PRDX4 expression was significantly lower in RDC than in POA, whereas inflammatory markers and the density of multinucleated osteoclast-like cells were significantly higher. When the RDC cohort was analyzed internally, weak PRDX4 expression was significantly associated with strong 8-hydroxy-2'-deoxyguanosine (8-OHdG) expression, showing a significant inverse correlation. Strong PRDX4 expression was closely related to a lower empty lacunae burden and showed an exploratory association with osteoclast-like cell-rich remodeling changes within RDC. These findings suggest that reduced PRDX4 expression is associated with oxidative injury and may be linked to histopathological changes reflecting more advanced tissue injury. Therefore, PRDX4 may serve as a candidate tissue-level indicator associated with the local antioxidant response in RDC.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25153"},"PeriodicalIF":2.2,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox biology in periodontal inflammation, tissue repair, and bone remodeling: Local-systemic interactions and therapeutic implications.","authors":"Gabriele Vanzela Monteiro, Erica Dorigatti de Avila, Joao Victor Soares Rodrigues, Joao Pedro Franco-Moura, Leticia Helena Theodoro, Rafael Scaf de Molon","doi":"10.14670/HH-25-152","DOIUrl":"https://doi.org/10.14670/HH-25-152","url":null,"abstract":"<p><p>Periodontitis is a biofilm-associated, host-mediated inflammatory disease in which persistent immune activation, extracellular matrix degradation, defective repair, and inflammatory bone loss occur within an accessible tissue environment. Successful healing depends on the timely resolution of inflammation and restoration of tissue architecture; however, disruption of these processes contributes to chronic inflammatory diseases characterized by persistent inflammation, impaired regeneration, and progressive tissue destruction. Among the mechanisms governing these outcomes, redox biology has emerged as an important regulator linking inflammation, cellular function, and tissue remodeling. Reactive oxygen species (ROS) are not solely damaging metabolic byproducts; at controlled levels, they support host defense, cell migration, angiogenesis, and reparative signaling. By contrast, excessive, sustained, or compartmentally dysregulated ROS production promotes oxidative distress, amplifies inflammatory signaling, disrupts epithelial and extracellular matrix integrity, impairs vascular and stromal cell function, enhances osteoclastogenesis, and suppresses osteoblast activity. Periodontal inflammation may also contribute to systemic oxidative and inflammatory burden through circulating mediators, microbial products, and metabolic-immune interactions. This review integrates histological, cellular, metabolic, and bone-remodeling perspectives to propose a periodontitis-centered basis in which the biological effect of ROS depends on their molecular identity, source, concentration, subcellular location, and duration. In addition, current redox-based therapeutic strategies, including antioxidants, antimicrobial photodynamic therapy, and ozone-based approaches are discussed together with their translational limitations and future perspectives. Understanding how redox mechanisms influence tissue architecture and repair may provide new opportunities for the development of targeted therapeutic strategies aimed at restoring tissue homeostasis and improving regenerative outcomes in periodontitis.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25152"},"PeriodicalIF":2.2,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sympathetic innervation of renal cell carcinomas and their environment, a pilot study.","authors":"Paul C M S Verhagen, Claire Mackaaij, Coert Ridderhof, Peter-Paul M Willemse, Trudy Jonges, Marian Clahsen van Groningen, Cindy Cleypool","doi":"10.14670/HH-25-151","DOIUrl":"https://doi.org/10.14670/HH-25-151","url":null,"abstract":"<p><strong>Objectives: </strong>Sympathetic nerves are a common feature in tumors; in the tumor microenvironment and in mouse models, they have been implicated in tumor initiation and progression. Clinical studies report an association between increased nerve density and adverse tumor characteristics in various carcinomas. So far, no studies have been published in renal cell carcinoma (RCC). The aim of this study is to quantify sympathetic nerves in RCC and its environment.</p><p><strong>Materials and methods: </strong>We quantified sympathetic nerve density in 10 T1a RCCs, 5 metastatic lesions, and 8 normal kidney tissues. Histopathological analysis and immunohistochemistry with antibodies against tyrosine hydroxylase (TH) were performed.</p><p><strong>Results: </strong>In normal kidney, autonomic nerves were mainly sympathetic. Within the T1a tumors, the percentage of TH-positive pixels of sympathetic nerves was low (0.03 +/- 0.05), and very low in metastases (0.001 +/- 0.003). A remarkable high-density pattern of sympathetic fibers was found in the vicinity of two T1a tumors. More distant (> 2mm), the percentage of TH-positive pixels was similar to that of controls (0.11 +/- 0.10).</p><p><strong>Conclusion: </strong>We observed a low density of sympathetic nerves within T1a renal tumors and metastatic lesions compared with normal kidney tissue. An increased density of sympathetic nerves was seen in the direct vicinity of two tumors. These preliminary results in this small pilot cohort suggest that in RCC, increased sympathetic nerve density may be encountered in the tumor environment but not the tumor itself.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25151"},"PeriodicalIF":2.2,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xiaoqinglong decoction improves chronic obstructive pulmonary disease by modulating PI3K/AKT-NRF2/NF-κB-mediated senescence-associated phenotypes.","authors":"Yanjun Ling, Xiao Zou","doi":"10.14670/HH-25-150","DOIUrl":"https://doi.org/10.14670/HH-25-150","url":null,"abstract":"<p><strong>Objective: </strong>Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disorder with limited therapeutic options. We aimed to investigate whether Xiaoqinglong decoction (XQLD) alleviates COPD by modulating senescence-associated phenotypes via the PI3K/AKT-NRF2/NF-κB pathway.</p><p><strong>Methods: </strong>COPD rat models were established by cigarette smoke exposure, lipopolysaccharide (LPS) administration, and cold stimulation, followed by gavage of XQLD (2 mL/day) for 14 days. <i>In vitro</i> COPD models were induced in A549 cells using LPS plus cigarette smoke extract, then treated with 1 mg/mL XQLD for 28h, with or without PI3K overexpression. XQLD compositions were analyzed. <i>In vivo</i>, pulmonary function, bronchoalveolar lavage fluid (BALF) cell counts, histopathology, collagen deposition, and apoptosis were assessed. <i>In vitro</i>, cell apoptosis and viability were assessed. Both animal and cell experiments detected senescence-associated secretory phenotype (SASP) markers and PI3K/AKT-NRF-2/NF-κB pathway-related protein expression.</p><p><strong>Results: </strong>XQLD's main components were alkaloids, monoterpene glycosides, flavonoid glycosides, triterpene saponins, amino acids, and organic acids. XQLD improved pulmonary function, reduced macrophage, neutrophil, and lymphocyte numbers in BALF, and relieved lung histopathological damage, collagen deposition, and apoptosis in COPD rats. <i>In vitro</i>, XQLD promoted viability but inhibited apoptosis in COPD cells. Animal and cell experiments showed that XQLD decreased SASP markers (TNF-α/IL-1β/IL-8/IL-6/P16/P21/P53/MMP-9/MMP-12), PI3K/AKT/NF-κB p65/IκB phosphorylation, and Keap1 expression, but increased NRF-2, HO-1, and NQO-1 levels. However, these effects of XQLD on COPD were abrogated by PI3K overexpression.</p><p><strong>Conclusions: </strong>XQLD attenuates senescence-associated phenotypes in COPD by modulating the PI3K/AKT-NRF2/NF-κB pathway, providing a novel mechanistic insight and highlighting this pathway as a potential therapeutic target for COPD.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"25150"},"PeriodicalIF":2.2,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}