Histology and histopathology最新文献

{"title":"Artificial intelligence for detection, grading, and prognostication in prostate cancer pathology: A scoping review.","authors":"Ranjitha Pratap Nair, Wei Du, Lin Mei, Shunsuke Koga","doi":"10.14670/HH-25-059","DOIUrl":"10.14670/HH-25-059","url":null,"abstract":"<p><p>Artificial intelligence (AI) has been transforming many aspects of medical care. In prostate cancer, ongoing progress in AI has improved research and patient care. Recent advances in machine learning and deep learning have produced tools that help diagnose cancer, assess risk, and predict outcomes. In screening, AI-based risk calculators improve detection and help avoid unnecessary biopsies. Deep learning algorithms, particularly convolutional neural networks, have demonstrated expert-level performance in pathology, identifying malignancy and assigning Gleason grades with high accuracy. These tools also streamline workflow, flagging challenging cases for review and quantifying prognostic markers, such as Ki-67 and cribriform patterns. In addition, AI-based models can predict molecular alterations, microsatellite instability, and lymph node metastasis directly from histology images, providing cost-effective alternatives to traditional assays. The development of multimodal models integrates digital pathology and clinical parameters, enabling personalized treatment recommendations and improved outcome prediction. Natural language processing and large language models further expand AI's potential, facilitating information extraction from clinical notes and enhancing patient education. Despite these advances, most studies remain retrospective with heterogeneous endpoints. Performance often drops when models are tested at new sites because of differences in patient populations and slide preparation. Access to large, well-annotated datasets is limited, and technical variation hampers reproducibility. To move toward clinical use, the field needs prospective, multicenter validation, preanalytical and analytical standardization, and clear reporting of failure modes and human oversight. Emerging approaches, including self-supervised pretraining, transformer-based image models, and language-vision systems, are likely to improve generalization and support more personalized care.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1493-1506"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432547","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":"Beyond cytoskeletal regulation: Rho-associated, coiled-coil-containing protein kinase 2 in kidney inflammation and fibrosis.","authors":"Keiichiro Matoba","doi":"10.14670/HH-25-047","DOIUrl":"10.14670/HH-25-047","url":null,"abstract":"<p><p>Chronic kidney disease (CKD), histologically defined by glomerulosclerosis, tubular atrophy, interstitial fibrosis, and capillary rarefaction, represents a profound challenge in cellular pathology. This review synthesizes recent advances to position Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2) as a master regulator of maladaptive cellular remodeling in CKD. We delineate the compartment-specific histopathological roles of ROCK2, demonstrating its function as a central signaling integrator that transduces mechanical, metabolic, and inflammatory stimuli into a convergent profibrotic phenotype. At the cellular level, ROCK2 activation drives podocyte foot process effacement and mesangial matrix expansion in the glomerulus, induces metabolic reprogramming and transcriptional dysregulation in tubular epithelia, disrupts endothelial junctional integrity in the microvasculature, and promotes myofibroblast transdifferentiation and immune-mediated scarring in the interstitium. Therapeutically, isoform-selective ROCK2 inhibition with agents like belumosudil demonstrates compelling efficacy in preclinical models, attenuating hallmark histopathological lesions. Translating these findings requires biomarker-driven patient stratification and innovative kidney-targeted delivery systems to maximize effectiveness and minimize systemic effects. Future research must ultrastructurally localize ROCK2 within human kidney niches, delineate its cell-type-specific effector networks, and validate its role as a therapeutic target to halt or reverse the characteristic microscopic progression of CKD.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1459-1469"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149666","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":"Tyrosine protein kinase ABL1 regulates the mTOR/ULK1 pathway to alleviate postoperative cognitive dysfunction in aged mice.","authors":"Chanjuan Chen, Jingwen Hao, Yuan Liu, Qi Wan","doi":"10.14670/HH-25-043","DOIUrl":"10.14670/HH-25-043","url":null,"abstract":"<p><strong>Background: </strong>Postoperative cognitive dysfunction (POCD) is a common and serious complication in older adult patients. While the tyrosine kinase ABL1 has been implicated in neurodegenerative diseases, its specific role in POCD remains unexplored. This study aims to investigate whether ABL1 influences POCD in aged mice by regulating microglial autophagy and neuroinflammation via the mTOR/ULK1 pathway.</p><p><strong>Methods: </strong>An aged mouse model of POCD was established, and ABL1 silencing and 3-Methyladenine (3-MA) were used to intervene in mice. The Novel Object Recognition Test (NORT) assessment and water maze experiment were conducted. qRT-PCR quantified the mRNA levels of inflammatory cytokines, hippocampal damage was assessed by immunofluorescence, and western blot analyzed the protein expression of autophagy-related genes and the mTOR/ULK1 pathway. Co-Immunoprecipitation (CO-IP) was used to detect the binding of ABL1 to mTOR. <i>In vitro</i> experiments used microglial cells, where <i>ABL1</i> silencing and rapamycin (Rapa) were used to construct a cellular model and conduct relevant cell experiments.</p><p><strong>Results: </strong><i>ABL1</i> silencing or 3-MA rescued cognitive deficits in aged POCD mice, concurrently mitigating neuroinflammation, microglial activation, and aberrant autophagy in the hippocampus. We established <i>ABL1</i> as a direct binding partner of mTOR. Silencing <i>ABL1</i> activated the <i>mTOR</i> pathway, leading to <i>ULK1</i> inhibition and suppression of autophagic activity. Consistent with these <i>in vivo</i> results, <i>ABL1</i> knockdown in microglia attenuated pro-inflammatory responses, inhibited autophagy, and conferred protection against neuronal damage.</p><p><strong>Conclusions: </strong><i>ABL1</i> exacerbates POCD in aged mice by promoting microglial autophagy and neuroinflammation through the <i>mTOR/ULK1</i> signaling pathway. Targeted inhibition of <i>ABL1</i> may represent a novel therapeutic strategy for preventing or treating POCD.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1541-1553"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112994","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":"SOX2 and cytokeratins 5, 8 and 18 as potential stem cell biomarkers in botryoid odontogenic, lateral periodontal and gingival cysts.","authors":"Robert S Redman, John R Basile, James T Castle","doi":"10.14670/HH-25-068","DOIUrl":"10.14670/HH-25-068","url":null,"abstract":"<p><p>The aim of this study was to compare the immunohistochemical expression of SOX2 and cytokeratins (CKs) 5, 8 and 18 in the lateral periodontal cyst (LPC) and gingival cyst of the adult (GCA) with the more aggressive botryoid odontogenic cyst (BOC), to evaluate diagnostic or prognostic utility.</p><p><strong>Methods: </strong>Sections from archival paraffin blocks were processed for immunohistochemical localization of SOX2 and CKs 5, 8 and 18. Sections from 6 odontogenic keratocysts (OKCs) were included for comparison with a cyst that enlarges more rapidly and has a higher rate of recurrence than most other odontogenic cysts. Samples consisted of 12 BOCs, 6 GCAs, 6 LPCs, and 6 OKCs for the CKs, and 9 BOCs, 4 GCAs, 6 LPCs and 6 OKCs for SOX2.</p><p><strong>Results: </strong>In the gingival epithelium in the GCA sections, all four antibodies labeled all cells in the basal cell layer, diminishing progressively through the intermediate layers to no or few cells in the superficial layers, indicative of stem cells and transit amplifying cells residing in the basal cell layer. In most BOCs, GCAs, LPCS and OKCs, antibodies to SOX2 and CK 5 displayed the same pattern as in the gingiva. However, CK 8 labeled all cell layers in all cysts except two OKCs and CK 18 labeled all except the basal cell layer in almost half the cysts. SOX2 was labile and in some older specimens there was no or a faint reaction which disproportionately affected the basal cell layer in the OKCs. There were no differences in the labeling patterns of any antibodies between the BOCs and the combined GCAs and LPCs (chi-square).</p><p><strong>Conclusions: </strong>Only the labeling patterns of SOX2 and CK 5 were consistent with that of a stem cell biomarker. A role in the more aggressive behavior of the BOC could not be drawn from the results with any of the antibodies.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1515-1526"},"PeriodicalIF":2.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147521164","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":"Application of the ultrasonic oscillation flotation method in paraffin section preparation.","authors":"Min Zhang, Yue Chen, Lü Ren, Jinzhi Xia, Lu Tao, Jianguo Hu, Jing Li, Xiaofeng Zhang, Zhijun Geng, Yueyue Wang, Xue Song","doi":"10.14670/HH-25-053","DOIUrl":"10.14670/HH-25-053","url":null,"abstract":"<p><strong>Objective: </strong>To enhance the quality and efficiency of paraffin-embedded pathological section preparation, this study aims to investigate the potential benefits of utilizing the ultrasound oscillation flotation method (UOFM) for section spreading.</p><p><strong>Methods: </strong>Specimens of various tissue types were processed using both the conventional and UOFM for section spreading. The presence of wrinkles or damage during this process was assessed through HE staining, with the number of wrinkles being quantified. The optimal frequency and power density for section spreading were determined by evaluating the qualified rate of sections at various frequencies and power densities, and the average time required for section spreading was compared between the two methods.</p><p><strong>Results: </strong>The results showed that pathological sections of various tissue types rarely showed paraffin dissolution and section breaking after the UOFM. HE staining also revealed that the group exhibited significantly reduced wrinkling and a more intact tissue structure compared with the conventional method group (<i>p</i><0.05). Statistical analysis further indicated that the highest rate of section qualification was achieved when employing a frequency of 33 kHz with a power density of 60% or a frequency of 40 kHz with a power density of 75% (<i>p</i><0.05). Additionally, the mean duration of section spreading in the group utilizing the UOFM was significantly reduced (<i>p</i><0.05).</p><p><strong>Conclusions: </strong>The UOFM effectively maintains the structural integrity of paraffin pathological sections, significantly enhancing the quality of sections and optimizing section preparation efficiency.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1451-1457"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343464","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":"Astragalus polysaccharide protects against neuron degeneration and mitochondrial dysfunction in Parkinson's disease by upregulating CEND1.","authors":"Zewei Cong, Chan Li, Mengqin Sun, Yan Yu, Xianmei Zhang","doi":"10.14670/HH-25-033","DOIUrl":"10.14670/HH-25-033","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a chronic neurodegenerative disorder featuring dopaminergic neuron loss, which is associated with mitochondrial dysfunction. Astragalus polysaccharide (APS) extracted from <i>Astragalus membranaceus</i> possesses antioxidant, anti-inflammatory, and neuroprotective properties. APS was previously revealed to exert neuroprotective effects in experimental PD models. However, the underlying mechanism remains poorly understood. Therefore, our study was designed to reveal the molecular mechanism through which APS exerts neuroprotective effects in PD.</p><p><strong>Methods: </strong>SH-SY5Y cells were treated with 6-hydroxydopamine (6-OHDA) to induce the <i>in vitro</i> model of PD. 6-OHDA-treated SH-SY5Y cells were further transfected with sh-CEND1 and treated with APS to assess whether APS alleviates 6-OHDA-induced neurotoxicity through regulating CEND1. Cell viability, apoptosis, intracellular ROS levels, mitochondrial membrane potential (MMP), and the levels of dopaminergic neuronal markers and mitochondrial biogenesis-related proteins in SH-SY5Y cells were evaluated through a CCK-8 assay, flow cytometry, DCFH-DA staining, JC-1 staining, and western blotting. Finally, <i>CEND1</i>-knockout (CEND1-KO) mice were used to confirm whether APS exhibits the neuroprotective effects via a CEND1-dependent mechanism. Behavior tests, immunohistochemical staining, and western blotting were performed to examine mouse motor dysfunction, neuronal injury, and mitochondrial dysfunction.</p><p><strong>Results: </strong>6-OHDA downregulated CEND1 expression in SH-SY5Y cells and PD mice, which, however, was reversed after APS treatment. CEND1 knockdown aggravated while CEND1 overexpression ameliorated 6-OHDA-induced SH-SY5Y cell injury, apoptosis, ROS production, and mitochondrial dysfunction. The preventive effects of CEND1 upregulation against 6-OHDA-induced neuron degeneration and mitochondrial dysfunction were attributed to the activation of the PI3K/AKT and AMPK/SIRT1/PGC-1α signaling pathways. Besides, APS alleviated 6-OHDA-induced SH-SY5Y cell injury and mitochondrial dysfunction, while silencing of CEND1 abrogated the neuroprotective effects of APS <i>in vitro</i>. APS administration successfully improved motor deficits, neuronal injury, and mitochondrial impairments in WT (wild-type) mice, but failed to protect against PD in CEND1-KO mice.</p><p><strong>Conclusion: </strong>APS exerts its neuroprotective effects in PD by preventing mitochondrial dysfunction through increasing CEND1 expression.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1399-1414"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970807","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":"Clinical-histological and genetic features of rare variants of melanoma.","authors":"Gerardo Cazzato, Francesco Fortarezza, Costantino Ricci, Mario Della Mura, Giuseppe Ingravallo, Angelo Paolo Dei Tos, Carlos W Barría, Antonina Kalmykova, Philip McKee","doi":"10.14670/HH-25-041","DOIUrl":"10.14670/HH-25-041","url":null,"abstract":"<p><p>Melanoma is traditionally classified into a limited number of common clinicopathologic subtypes; however, routine clinical and histopathologic practice reveals a broad spectrum of rare variants and unusual morphologic patterns that pose significant diagnostic and therapeutic challenges. These uncommon melanomas may closely mimic benign melanocytic proliferations or non-melanocytic neoplasms, present with subtle or atypical clinical and dermoscopic features, and exhibit distinctive biologic behavior and treatment responses. Consequently, their clinical impact is disproportionate to their low incidence. This narrative review provides an updated and integrated overview of rare primary melanoma subtypes, including desmoplastic melanoma, nevoid melanoma, Spitz melanoma, melanoma ex blue nevus, and primary dermal melanoma, as well as uncommon histologic variants such as rhabdoid, metaplastic (osteogenic and chondrogenic), myxoid, small cell, balloon/clear cell, signet-ring cell, and plexiform melanoma. In addition, rare combined cutaneous tumors containing both melanomatous and epithelial components are discussed. For each entity, we summarize current evidence on epidemiology, clinical and dermoscopic presentation, histopathologic features, immunohistochemical profiles, and molecular alterations, with particular emphasis on key diagnostic pitfalls and differential diagnoses. Advances in molecular pathology have refined the classification of these rare melanomas, enabling more precise integration of morphology, immunophenotype, and genomic data, with direct implications for prognosis, staging, and therapeutic decision-making. Finally, we review available data on management strategies, including surgery, sentinel lymph node biopsy, radiotherapy, targeted therapy, and immunotherapy. By synthesizing current knowledge and highlighting practical diagnostic and therapeutic considerations, this review aims to assist pathologists and clinicians in navigating the \"grey zones\" of melanoma diagnosis, ultimately supporting more accurate classification and more personalized patient care.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1317-1338"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146062680","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":"Aldose reductase as a regulator of ocular pathology: Mechanisms and therapeutic potential.","authors":"Laman Mirzaliyeva, Pei-Kang Liu, Dimitrios Stavropoulos, Kun-Che Chang","doi":"10.14670/HH-25-045","DOIUrl":"10.14670/HH-25-045","url":null,"abstract":"<p><p>Aldose reductase (AR), the rate-limiting enzyme of the polyol pathway, converts glucose to sorbitol using NADPH and becomes markedly overactive under hyperglycemic conditions. Its widespread expression in ocular tissues links AR to numerous eye disorders through sorbitol accumulation, microglial activation, NADPH depletion, oxidative stress, and increased formation of advanced glycation end products. These mechanisms contribute to the development of diabetic retinopathy, cataract, glaucoma, and other optic neuropathies, conditions that affect a large portion of the population and carry a substantial risk of progressing to vision loss if left untreated. The central involvement of AR in these processes has driven extensive development of aldose reductase inhibitors (ARIs), which reduce sorbitol buildup, oxidative stress, VEGF expression, and microglial activation. Thus, clarifying the functions of AR and therapeutically targeting this pathway remains essential for advancing strategies to prevent or slow the progression of ocular disease.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1339-1347"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118910","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":"Prognostic significance of ACADL and MCM2 in meningiomas: Current evidence and clinical implications.","authors":"Alberto Pietrantoni, Fabio Agistri, Valeria Barresi","doi":"10.14670/HH-25-046","DOIUrl":"10.14670/HH-25-046","url":null,"abstract":"<p><p>This review summarizes the current evidence on the expression and prognostic significance of acyl-CoA dehydrogenase long-chain (ACADL) and minichromosome maintenance 2 (MCM2) in meningiomas. Meningiomas, which comprise approximately 41% of intracranial tumors, are classified by the World Health Organization into 15 histological subtypes and three grades of malignancy. However, owing to the biological heterogeneity within tumors of the same grade, alternative classifications based on molecular features have been proposed. One of these classifies meningiomas into four prognostically relevant molecular groups: immunogenic, benign <i>NF2</i>-wildtype, hypermetabolic, and proliferative. The latter two groups have the worst clinical outcomes and are enriched in ACADL and MCM2 expression, suggesting their potential as immunohistochemical surrogates. The revision of the current literature on the expression of these markers in meningiomas indicates their likely unsuitability as surrogates for molecular groups. However, MCM2 expression was consistently associated with aggressive histopathological features and reduced recurrence-free survival, emerging as a promising independent prognostic marker. ACADL also showed negative prognostic relevance, but with limited data, predominantly in grade 2 meningiomas. Both markers correlated with higher WHO grades but lacked standardized assessment criteria, limiting their clinical application. While ACADL and MCM2 immunoexpression does not reliably substitute molecular classification, MCM2, in particular, holds potential for routine prognostic use pending further validation and standardization of immunohistochemical protocols.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1349-1355"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142373","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":"Asiatic acid alleviates dexamethasone-induced muscle atrophy through regulating the Sirt1/PGC-1α/FOXO3 pathway.","authors":"Dongfang Ji, Mingxin Cui, Chao Tian, Kaili Chen, Jing Shao","doi":"10.14670/HH-18-991","DOIUrl":"10.14670/HH-18-991","url":null,"abstract":"<p><strong>Background: </strong>Skeletal muscle atrophy, which results in muscular dysfunction and weakness, is associated with various factors, including aging, sepsis, chronic diseases, and long-term glucocorticoid therapy. Although asiatic acid exhibits multiple biological activities and can activate the Sirt1 signaling pathway, an important regulator of skeletal muscle function,itsrole in muscle atrophy remains unclear.</p><p><strong>Methods: </strong>C2C12 myotubes were treated with 10 μM dexamethasone,with or without designated concentrations of asiatic acid. Subsequently, cell viability, apoptosis, differentiation markers (MyHC and myogenin), levels of atrophy-related proteins (MAFbx, MuRF1), and the Sirt1/PGC-1α/FOXO3 pathway were analyzed. Moreover,the underlyingmechanismswere further explored through inhibition of Sirt1 using the selective inhibitor EX-527 or short hairpin RNA <i>in vitro</i>. <i>In vivo</i>, muscle atrophy was induced via intraperitoneal injections of 20 mg/kg dexamethasone, and 50 mg/kg asiatic acid was administered by oral gavage. Body weight, muscle strength, gastrocnemius muscle mass, histological changes, and atrophy- and Sirt1/PGC-1α/FOXO3 pathway-associated proteins were assessed.</p><p><strong>Results: </strong>Asiatic acid elevated cellviability, inhibited apoptosis, increased MyHC and myogeninprotein contents, and suppressed MAFbx and MuRF1 proteinlevels in dexamethasone-treated C2C12 myotubes. Moreover, asiatic acid activated the Sirt1/PGC-1αp athwayand inactivated FOXO3. Inhibition of Sirt1 attenuated the influence of asiatic acid in a muscle atrophy cell model. <i>In vivo</i>, asiatic acid increased body weight and gastrocnemius muscle mass, improved muscle strength and structural damage of gastrocnemius muscles, suppressed MAFbx and MuRF1 protein contents, and regulated the Sirt1/PGC-1α/FOXO3 pathway.</p><p><strong>Conclusions: </strong>Asiatic acid can improve dexamethasone-induced muscle atrophy via regulating the Sirt1/PGC-1α/FOXO3 pathway. Therefore, asiatic acid might be a potential therapeutic agent for muscle atrophy.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1387-1397"},"PeriodicalIF":2.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124588","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}