Acta histochemica最新文献

{"title":"Neurochemical heterogeneity of ChAT-immunoreactive neurons in the basal forebrain cholinergic nuclei and striatum in reference to CGRP, CCK, and calcium-binding proteins","authors":"Mirza Mienur Meher ,&nbsp;Marya Afrin ,&nbsp;Mir Rubayet Jahan ,&nbsp;Kanako Nozaki ,&nbsp;Koh-hei Masumoto ,&nbsp;Akie Yanai ,&nbsp;Md Nabiul Islam","doi":"10.1016/j.acthis.2025.152291","DOIUrl":"10.1016/j.acthis.2025.152291","url":null,"abstract":"<div><div>Cholinergic neurons in the basal forebrain cholinergic nuclei (BFCN) and neostriatum (CPu) play key roles in learning, attention, and motor control. The loss of cholinergic neurons causes major neurodegenerative diseases such as Alzheimer’s disease. This study aimed to elucidate the molecular diversity of choline acetyltransferase immunoreactive (ChAT-ir) neurons in these brain regions. We performed immunohistochemistry to determine the co-expression of ChAT-ir neurons with two neuropeptides, calcitonin gene-related peptide (CGRP) and cholecystokinin (CCK), as well as three calcium-binding proteins, such as calbindin, calretinin, and parvalbumin, in the adult mouse brain. The results showed that ChAT, calbindin, CGRP and CCK were strongly expressed in the BFCN, including medial septal nucleus (MS), nucleus of vertical limb and horizontal limb of the diagonal band of Broca (VDB and HDB), substantia innominata basal part (SIB), and in the caudate putamen (CPu). CGRP and CCK showed a high immunoreactive co-expression with ChAT, especially in the HDB and CPu. Calbindin immunoreactivity was widely present and coincided with ChAT in the VDB, HDB, and CPu. However, calretinin immunoreactivity showed a selective co-expression with ChAT in the VDB, SIB, and CPu. Although parvalbumin immunoreactivity was observed throughout the BFCN and CPu, but there was no co-expression between ChAT and parvalbumin. The neurochemical diversity of ChAT-ir neurons in the BFCN and neostriatum suggests the specialized functions of cholinergic neurons across different circuits, especially by modulating CGRP, CCK, or calbindin. These results could provide new insight into cholinergic modulation throughout the BFCN and striatum.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 4","pages":"Article 152291"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009844","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":"Neuroprotective effect of Urolithin A via downregulating VDAC1-mediated autophagy in Alzheimer's disease","authors":"Bensi Zhang ,&nbsp;Xiujun Zhang ,&nbsp;Waleephan Treebupachatsakul ,&nbsp;Rungusa Pantan ,&nbsp;Natnicha Kampan ,&nbsp;Manussabhorn Phatsara ,&nbsp;Chun Shi ,&nbsp;Suteera Narakornsak","doi":"10.1016/j.acthis.2025.152290","DOIUrl":"10.1016/j.acthis.2025.152290","url":null,"abstract":"<div><h3>Background</h3><div>Amyloid β (Aβ) accumulation in the brains of patients with Alzheimer's disease (AD) contributes to cognitive impairment and neuronal damage. Urolithin A (UA), a gut microbiota–derived metabolite of ellagic acid, has been reported to cross the blood-brain barrier to exert anti-inflammatory and anti-oxidation effects in the brain. However, the molecular mechanisms of UA in AD were still unclear. This study aims to explore the neuroprotective effect and mechanism of UA on APP/PS1 mice and Aβ_1–42-injured N2a and PC12 cells.</div></div><div><h3>Methods</h3><div>In this study, Morris water maze was used to detect the cognitive function. Immunofluorescence was used to detect the deposition of Aβ and the expression of voltage-dependent anion channel 1 (VDAC1) in the brains of APP/PS1 mice. Western blotting was used to detect the expression of VDAC1, AMPK pathway, PI3K pathway and autophagy-related proteins. CCK8 was used to detect the viability of Aβ_1–42-injured cells.</div></div><div><h3>Results</h3><div>In this research, we found that UA improved cognitive dysfunction and reduced Aβ deposition in APP/PS1 mice. Furthermore, UA activated autophagy and upregulated the levels of autophagy-related proteins in both APP/PS1 mice and Aβ_1–42-injured N2a and PC12 cells. At the same time, UA down-regulated the phosphorylation level of PI3K/AKT/mTOR and up-regulated the phosphorylation level of AMPK in APP/PS1 mice and Aβ_1–42-injured N2a cells and PC12 cells. In addition, UA down-regulated VDAC1, consistent with the effect of VDAC1 antagonist DIDS (4′-diisothiocyano-2,2′-disulfonic acid stilbene). Importantly, the UA-induced activation of autophagy and modulation of the PI3K and AMPK pathways were reversed by VDAC1 overexpression.</div></div><div><h3>Conclusion</h3><div>These findings demonstrated that UA down-regulated VDAC1 played a key neuroprotective role on AD by inhibiting the PI3K/AKT/mTOR pathway and activating the AMPK pathway to promote autophagy.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 4","pages":"Article 152290"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144921397","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":"Retraction notice to \" Paeonol antagonizes oncogenesis of osteosarcoma by inhibiting the function of TLR4/MAPK/NF-?B pathway\" [Acta Histochem. 122 (2020) 151455]","authors":"Jianguo Zhou ,&nbsp;Qinglin Liu ,&nbsp;Rui Qian,&nbsp;Shiwei Liu,&nbsp;Weiquan Hu,&nbsp;Zhenyu Liu","doi":"10.1016/j.acthis.2025.152295","DOIUrl":"10.1016/j.acthis.2025.152295","url":null,"abstract":"","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 4","pages":"Article 152295"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211295","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":"POSTN promotes ferroptosis and contributes to the pathogenesis of IgA nephropathy via GPX4 downregulation","authors":"Wang Jia ,&nbsp;Yonggui Wu","doi":"10.1016/j.acthis.2025.152296","DOIUrl":"10.1016/j.acthis.2025.152296","url":null,"abstract":"<div><div>IgA nephropathy (IgAN) is a prevalent glomerular disease characterized by mesangial deposition of IgA1-containing immune complexes, yet its underlying molecular mechanisms remain incompletely understood. In this study, we integrated bioinformatics analyses of two public datasets (GSE104948 and GSE93798) to identify key differentially expressed genes (DEGs) associated with IgAN. Periostin (POSTN) emerged as a hub gene, exhibiting significant upregulation in IgAN samples and correlating with histopathological severity. Functional enrichment revealed that overlapping DEGs are involved in extracellular matrix organization, immune response, and signaling pathways relevant to renal pathology. Immunohistochemical and immunofluorescence analyses confirmed increased POSTN and decreased GPX4 expression in renal biopsies from IgAN patients, indicating enhanced ferroptosis. In vitro, IgA1 stimulation of human mesangial cells (HMCs) elevated POSTN expression and induced ferroptosis, evidenced by increased oxidative stress, mitochondrial damage, and reduced cell viability. Knockdown of POSTN ameliorated these effects by restoring glutathione levels and reducing lipid peroxidation, while POSTN overexpression exacerbated ferroptosis. Notably, treatment with the ferroptosis inhibitor ferrostatin-1 reversed POSTN-induced cellular damage. Our findings suggest that POSTN promotes IgAN progression by facilitating ferroptosis through GPX4 downregulation, highlighting a novel pathogenic mechanism. Targeting POSTN-mediated ferroptosis may provide promising therapeutic strategies for IgAN. This study advances our understanding of IgAN molecular pathology and offers potential biomarkers and intervention targets to improve patient outcomes.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 4","pages":"Article 152296"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462918","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":"Corrigendum to “Inducible gankyrin overexpression drives hepatocarcinogenesis in a liver-specific zebrafish model” [Acta Histochem. 127 (2025) 152280]","authors":"Yuxi Sun ,&nbsp;Zhiyuan Gong ,&nbsp;Yueh-Min Lin ,&nbsp;Jeng-Wei Lu","doi":"10.1016/j.acthis.2025.152281","DOIUrl":"10.1016/j.acthis.2025.152281","url":null,"abstract":"","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 4","pages":"Article 152281"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881816","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":"FoxO1 in skeletal muscle atrophy: Multifaceted regulatory mechanisms and therapeutic opportunities","authors":"Cheng-Ya Song ,&nbsp;Tian-Yi Zhou ,&nbsp;Han-Bo Shi ,&nbsp;Xin-Yi Li ,&nbsp;Kan Hong","doi":"10.1016/j.acthis.2025.152293","DOIUrl":"10.1016/j.acthis.2025.152293","url":null,"abstract":"<div><div>Skeletal muscle, which accounts for nearly 40 % of total body mass, serves as the primary effector organ for locomotion, metabolism, and thermoregulation. Skeletal muscle atrophy, a common condition associated with aging, disease, and disability, significantly compromises patients’ quality of life. This review focuses on the occurrence and progression of skeletal muscle atrophy. Forkhead box protein O1 (<em>FoxO1</em>) is a key regulatory factor that mediates pathological mechanisms through multidimensional molecular networks. It influences skeletal muscle metabolism via post-translational modifications (PTMs), dysregulated autophagy, an imbalanced inflammatory microenvironment, and the regulation of satellite cell function. Therapeutic strategies targeting <em>FoxO1</em>, such as resveratrol-induced <em>SIRT1</em> activation and miR-486 mimics, have shown promising results in preclinical models. This review highlights the central role of <em>FoxO1</em> in molecular pathways, proposes a potential framework for addressing muscle atrophy, and offers new insights into the treatment of sarcopenia and related diseases.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 4","pages":"Article 152293"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118327","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":"Advancing triple-negative breast cancer therapy: 3D in vitro models to unravel drug resistance mechanisms and tumor microenvironment interactions","authors":"Gomathy Baskar ,&nbsp;Thirunavukkarasu Palaniyandi","doi":"10.1016/j.acthis.2025.152282","DOIUrl":"10.1016/j.acthis.2025.152282","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) poses considerable clinical challenges due to its aggressive nature, early metastasis, and limited treatment options. The simplified 2D models and the physiological differences in animal models often result in inconsistent responses to anticancer drugs. To tackle these challenges, three-dimensional (3D) in vitro bioengineered models that accurately replicate the <em>in vivo</em> tumor microenvironment (TME) have been developed, offering a more reliable platform for preclinical drug testing. Recent advancements in cell culture techniques have facilitated the creation of 3D models derived from patient tissues and tumors, which effectively mimic the native tissue environment and exhibit drug sensitivity and cytotoxicity behaviors similar to those observed in vivo. It is increasingly acknowledged that the extracellular matrix and cellular diversity within the TME significantly influence the fate of cancer cells. Consequently, strategies to explore drug resistance mechanisms must account for both microenvironmental factors and genetic mutations. This review examines 3D in vitro model systems that integrate microenvironmental influences to investigate drug resistance mechanisms in breast cancer. We discussed various bioengineered models, including spheroid-based, biomaterial-based (such as polymeric scaffolds and hydrogels), patient-derived xenograft (PDX), 3D bioprinting, and microfluidic chip-based models. Additionally, we discuss the relevance of these 3D models in understanding the effects of TME signals on drug response and resistance, as well as their potential for developing strategies to overcome drug resistance and optimize treatment regimens.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 4","pages":"Article 152282"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144858076","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":"Blood transfusion mediated tumor microenvironment remodeling in breast cancer","authors":"Qinan Yin ,&nbsp;Shunshun Zhang ,&nbsp;Mouna Ouchari ,&nbsp;Pei Wang ,&nbsp;Anshun Zhao ,&nbsp;Li Zeng ,&nbsp;Jingjing Wang ,&nbsp;Kaiyuan Yao ,&nbsp;Siya Tang ,&nbsp;Haodi Ma ,&nbsp;Anne-Catherine Girondin ,&nbsp;Hecai Yang ,&nbsp;Xuewei Zheng ,&nbsp;Zhifeng Qu","doi":"10.1016/j.acthis.2025.152289","DOIUrl":"10.1016/j.acthis.2025.152289","url":null,"abstract":"<div><div>Blood transfusions play a critical role in breast cancer management, particularly in addressing perioperative blood loss and chemotherapy-induced anemia. However, emerging evidence suggests that transfusions may adversely affect oncologic outcomes by inducing transfusion-related immunomodulation (TRIM) and altering the tumor microenvironment (TME). TRIM suppresses cytotoxic immune responses, potentially facilitating tumor progression—especially in aggressive subtypes such as triple-negative breast cancer (TNBC) and HER2-positive cancers. Additionally, transfusions can paradoxically exacerbate tumor hypoxia by increasing blood viscosity and impairing microvascular perfusion, thereby reducing the effectiveness of chemotherapy, radiotherapy, and immunotherapy. This review examines the dual role of blood transfusions in breast cancer, emphasizing both their clinical benefits and potential risks. We analyze their impact on treatment resistance and tumor progression and discuss strategies to mitigate associated risks, including leukoreduction, erythropoiesis-stimulating agents (ESAs), intravenous iron supplementation, and blood conservation techniques. Furthermore, we highlight the importance of personalized transfusion approaches guided by tumor subtype, immune status, and relevant biomarkers such as tumor-infiltrating lymphocytes (TILs), PD-L1 expression, and circulating tumor DNA (ctDNA). Future research should focus on optimizing transfusion timing, implementing biomarker-driven protocols, and developing immune-modulating interventions to counteract TRIM. A personalized, evidence-based transfusion strategy may ultimately enhance treatment efficacy and improve long-term outcomes in breast cancer care.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 4","pages":"Article 152289"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144889220","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":"Cancer-associated fibroblast-derived CCL5 enhanced aerobic glycolysis through upregulation of IP3R to promote breast cancer cell metastasis","authors":"Mingxiang Zhang ,&nbsp;Zhengzhi Zhu ,&nbsp;Guang Yang ,&nbsp;Yongyun Zhu","doi":"10.1016/j.acthis.2025.152292","DOIUrl":"10.1016/j.acthis.2025.152292","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to investigate whether cancer-associated fibroblast (CAF)-derived chemokine C-C motif ligand 5 (CCL5) promotes breast cancer (BC) cell metastasis by enhancing aerobic glycolysis via upregulation of IP3R.</div></div><div><h3>Methods</h3><div>Lentiviral vectors for CCL5 overexpression or knockdown were constructed, transfected into CAFs, and co-cultured with ZR-75–30 cells CCL5. Cell proliferation and apoptosis were assessed by CCK-8, cloning assay and flow cytometry. Cell migration and invasion were verified by scratch assay and Transwell assay. Co-IP verified the interactions between CCL5 and IP3R. The kit detects aerobic glycolysis-related indexes. western bloting detects CCL5, IP3R, glycolysis-related proteins, EMT-related proteins and metastasis-related proteins.</div></div><div><h3>Results</h3><div>Knockdown of CCL5 in CAFs and co-culture with breast cancer cells resulted in decreased cell proliferation, migration, and invasionCCL5, increased apoptosis, and attenuated aerobic glycolysis. Co-immunoprecipitation (Co-IP) assays revealed direct protein-protein interactions between CCL5 and IP3RCCL5. IP3R overexpression following CCL5 knockdown rescued breast cancer cell proliferative viability CCL5, restoration of migration and invasion abilities, and enhanced aerobic glycolysis.</div></div><div><h3>Conclusion</h3><div>CAF-derived CCL5 enhanced aerobic glycolysis in breast cancer cells by up-regulating IP3R expression, which in turn promoted their metastasis.</div></div><div><h3>Data Availability</h3><div>The data used to support the findings of this study are available from the corresponding author upon request.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 4","pages":"Article 152292"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118326","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":"S100A8 and S100A9-mediated keratinocyte affecting T lymphocyte immune imbalance through TLR4/NF-κ B in psoriasis","authors":"Yali He ,&nbsp;Jianxiao Xing ,&nbsp;Junqin Li ,&nbsp;Kaiming Zhang ,&nbsp;Xinhua Li","doi":"10.1016/j.acthis.2025.152297","DOIUrl":"10.1016/j.acthis.2025.152297","url":null,"abstract":"<div><div>Psoriasis is a chronic,immune-mediated inflammatory skin disorder characterized by recurrent thick plaque. As an alarmin of inflammation, the importance of S100A8 and S100A9 have already been confirmed to be associated with the development of chronic inflammation in diseases. However, the precise mechanisms of S100A8 and S100A9 in psoriasis remain unclear. Therefore,the aim of this study was to elucidate the effects and underlying mechanisms of S100A8 and S100A9 in psoriasis. In this study, we found that both S100A8 and S100A9 were highly expressed in cells treated with M5—a cytokine mixture containing IL-1α, IL-17A, IL-22, oncostatin M, and TNF-α—as well as in a mouse model of imiquimod (IMQ)-induced psoriasis. Meanwhile, S100A8 and S100A9 knockdown in normal human epidermal keratinocytes (NHEK) inhibited the proliferation of NHEK cells in psoriasis. To further investigate the effects of S100A8 and S100A9 on psoriatic inflammation, T cells were co-cultured with S100A8 and S100A9 knockdown NHEK cells, and S100A8 and S100A9 promoted the production of pro-inflammatory cytokines by T cells through activation of Toll-like receptor 4 (TLR4)/NF-κB signaling pathway. In particular, when the S100A8 and S100A9 inhibitor paquinimod was added to a mouse model of imiquimot-induced psoriasis, psoriatic dermatitis and inflammatory factors were reduced, and the expression of TLR4/NF-κB was also significantly reduced. In conclusion, this study illustrated that S100A8 and S100A9 participates in the pathogenesis of psoriasis by activating TLR4/NF-κB signaling pathways, thereby promoting psoriasis-associated skin inflammation, which suggested the potential role of S100A8 and S100A9 in the development of psoriasis and provided new insight into targeted therapies.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 4","pages":"Article 152297"},"PeriodicalIF":2.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145547789","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}