Acta Histochem. [JOURNAL]
Sun
200 papers
Optimizing the resolution-fidelity trade-off in SRRF nanoscopy for live-cell clathrin imaging.
Fang S, Liu L, Yang D … +4 more , Liu S, Yin W, Huang Q, Chen J
Acta Histochem · 2026 Mar · PMID 41483743 · Publisher ↗
Total internal reflection fluorescence microscopy (TIRFM) enables live-cell imaging of clathrin-coated pits (CCPs) but is diffraction-limited (∼250 nm), hindering visualization of their dense nanostructures (∼150 nm). Su...
Total internal reflection fluorescence microscopy (TIRFM) enables live-cell imaging of clathrin-coated pits (CCPs) but is diffraction-limited (∼250 nm), hindering visualization of their dense nanostructures (∼150 nm). Super-Resolution Radial Fluctuations (SRRF) provides computational super-resolution; however, unoptimized parameters can disrupt the critical balance between resolution and structural fidelity. Here, we establish a comprehensive parameter optimization framework for SRRF-based nanoscopy of live CCPs. Using multi-modal metrics in CLTA-GFP HeLa cells, we identify a ring radius of 1.0 as optimal, balancing resolution (full width at half maximum = 180 ± 29 nm, p < 0.05 vs. TIRFM) with fidelity (resolution-scaled Pearson = 0.935 ± 0.018). The temporal radiality pairwise product mean (TRPPM) mode achieved superior resolution (154 ± 30 nm) while maintaining fidelity metrics comparable to Temporal radiality average (TRA) mode. In contrast, temporal radiality auto-correlations (TRAC) introduced artifactual structures and reduced fidelity. Parameters such as "remove positivity constraint" and gradient weighting induced severe artifacts and should be avoided. This optimized framework resolves the resolution-fidelity trade-off, enabling robust nanoscale imaging of clathrin-mediated endocytosis in live cells.
Cisplatin treatment induces a shift toward a quiescent Ki-67⁻/CD44⁺/CD133⁺ cancer stem cell subpopulation in a tumorsphere model derived from a murine non-small cell lung cancer cell line.
Gonçalves BÔP, Almeida MR, Costa VV … +3 more , Del Puerto HL, Birbrair A, Lopes LMS
Acta Histochem · 2026 Mar · PMID 41477960 · Publisher ↗
Non-small cell lung cancer (NSCLC) exhibits substantial cellular and molecular heterogeneity, partly due to the presence of cancer stem cells (CSCs). CSCs can arise from a coordinated process known as epithelial-mesenchy...
Non-small cell lung cancer (NSCLC) exhibits substantial cellular and molecular heterogeneity, partly due to the presence of cancer stem cells (CSCs). CSCs can arise from a coordinated process known as epithelial-mesenchymal transition (EMT). EMT promotes a more aggressive phenotype, contributing significantly to tumor heterogeneity and drug resistance. Here, using state-of-the-art techniques-including confocal microscopy, flow cytometry, and transcript analysis-we investigated the cisplatin response of the LL/2 (LLC1) cell line cultured in both monolayer and tumorsphere (3D) models. Strikingly, LL/2 (LLC1) tumorspheres represent a model of cisplatin resistance, showing a remarkable increase in EMT and pluripotency mRNA regulators such as Zeb1, Zeb2, Snail, Twist, Tgfb1, Vimentin, FoxA2, Nanog, and Pou5f1 (Oct-4). Moreover, pseudotime trajectory analysis demonstrated that cisplatin treatment modulates a CSC-like phenotype differently in cells grown as monolayer versus tumorsphere. Our findings provide important insights into the role of cisplatin in NSCLC and highlight potential targets within the lung cancer microenvironment.
From membranes to medicine: Emerging insights into Ezrin's Role in human disease - A comprehensive overview.
Kumar H, Vashisht K, Kumari S … +4 more , Arora R, Ashawat P, Ashawat MS, Kushawaha SK
Acta Histochem · 2026 Mar · PMID 41477959 · Publisher ↗
Ezrin, a dynamic member of the Ezrin-Radixin-Moesin (ERM) family, plays a crucial role in orchestrating fundamental cellular functions, including membrane-cytoskeleton interactions, signal transduction, cell adhesion, mi...
Ezrin, a dynamic member of the Ezrin-Radixin-Moesin (ERM) family, plays a crucial role in orchestrating fundamental cellular functions, including membrane-cytoskeleton interactions, signal transduction, cell adhesion, migration, and immune regulation. Due to its broad functional repertoire, Ezrin has been increasingly recognized for its involvement in the pathogenesis of numerous human diseases, ranging from cancers and neurodegenerative disorders to renal and i conditions. In the central nervous system, Ezrin contributes to neurological homeostasis by preserving blood-brain barrier (BBB) integrity, modulating neuroinflammatory responses, and supporting synaptic plasticity and neuronal viability. Over the past few decades, scientific interest in Ezrin has grown significantly, as reflected by a marked increase in publications detailing its physiological and pathological roles. This review provides a comprehensive and uniquely alphabetized overview of Ezrin associations with a wide array of diseases, making it the first of its kind to catalog Ezrin biological relevance from A to Z. We examine its structural and biochemical characteristics, underscoring its potential as a diagnostic and prognostic biomarker, as well as an emerging therapeutic target. By addressing critical knowledge gaps, this review highlights Ezrin central role at the intersection of cancer biology, immunology, and neurotherapeutics.
Enhancing bone regeneration: The role of short fiber reinforced hydrogel with CO-controlled release on the osteogenic differentiation of bone marrow mesenchymal stem cells.
Dai S, Liang C, Fan X … +2 more , Li W, Zhao L
Acta Histochem · 2026 Mar · PMID 41456486 · Publisher ↗
The utilization of hydrogels in bone defect repair applications faces numerous challenges, while carbon dioxide (CO) demonstrates potential beneficial effects in bone healing processes. Based on this, the current study p...
The utilization of hydrogels in bone defect repair applications faces numerous challenges, while carbon dioxide (CO) demonstrates potential beneficial effects in bone healing processes. Based on this, the current study proposes a novel approach, namely, the deployment of a hydrogel scaffold laden with CO-controlled release material to promote bone defect repair, successfully proving its beneficial impact. By combining Poly-L-lactic Acid (PLLA), Gelatin Methacryloyl (GelMA), Nano-Hydroxyapatite (nHA), and Ammonium Bicarbonate (NH₄HCO₃) into a composite material, CO₂ may be produced in a 37°C PBS environment, primarily due to the decomposition of NH₄HCO₃. Additionally, the material can be thermosensitive, and the application of near-infrared (NIR) light may further enhance the CO₂ release by increasing the temperature locally, facilitating the decomposition of NH₄HCO₃. Bone marrow stromal cells (BMSCs) were cultured on the composite hydrogel to evaluate cell proliferation and osteogenic differentiation in vitro, while a rat cranial bone defect model was employed to assess in vivo bone regeneration. The research results indicate that this composite material significantly promotes BMSC cell proliferation and osteogenic differentiation and successfully accelerates bone healing in a rat cranial bone defect model. The substantiated insights and empirical evidence proffered herein lay a robust foundation for subsequent explorations in this vanguard domain of research.
An immunohistochemical study of Saussurea lappa nanoparticle on transformed cells in mice induced with benzo[a]pyrene for oral squamous cell carcinoma.
Budhy TI, Arundina I, Irmawati A … +5 more , Ming CH, Surboyo MDC, Moelyanto ASA, Dewanata P, Saqifa N
Acta Histochem · 2026 Mar · PMID 41443139 · Publisher ↗
BACKGROUND: Saussurea lappa, a plant used in traditional medicine, has shown promise in cancer treatment This study aimed to evaluate the therapeutic efficacy of Saussurea lappa nanoparticles using immunohistochemical an...
BACKGROUND: Saussurea lappa, a plant used in traditional medicine, has shown promise in cancer treatment This study aimed to evaluate the therapeutic efficacy of Saussurea lappa nanoparticles using immunohistochemical analysis in a benzo[a]pyrene-induced mouse model of oral squamous cell carcinoma (OSCC). The investigation focused on the expression of markers related to apoptosis (Bax, Caspase-3, BCL-2), inflammation (TNF-α), proliferation (Ki-67), and tumor suppression (p53). METHODS: A true experimental design was employed using male Mus musculus mice. OSCC was induced via exposure to benzo[a]pyrene. Following induction, mice were treated perorally with Saussurea lappa nanoparticles at doses of 50, 100, and 200 mg/kg body weight, while the control group received CMC-Na. Buccal mucosa samples were collected for immunohistochemical analysis, assessing dose-dependent effects of Saussurea lappa nanoparticles on the expression of Bax, Caspase-3, BCL-2, TNF-α, Ki-67 and p53. RESULT: Saussurea lappa nanoparticles demonstrated dose-dependent therapeutic effects in the OSCC mouse model. They significantly upregulated Bax, Caspase-3, TNF-α, and p53, while downregulating BCL-2 and Ki-67expression. The highest dose (200 mg/kg) showed the most pronounced effects, indicating enhanced apoptosis, reduced proliferation, and modulation of the inflammatory environment. CONCLUSION: These findings suggest that Saussurea lappa nanoparticles, particularly at a dose of 200 mg/kg BW, effectively promote apoptosis, inhibit cell proliferation, and suppress anti-apoptotic pathways. This highlights their potential as a promising therapeutic candidate for the treatment of oral mucosal malignancies.
Cellular landscape of reactive and neoplastic human lymph nodes in 3D.
Diederich VJ, Scharf S, Schäfer H … +3 more , Hartmann S, Hansmann ML, Wurzel P
Acta Histochem · 2026 Mar · PMID 41406636 · Publisher ↗
Lymph nodes function according to cellular and structural regulations. When these rules deviate from the benign equilibrium, dysregulations occur leading to the onset of diseases. In the development of malignant lymph no...
Lymph nodes function according to cellular and structural regulations. When these rules deviate from the benign equilibrium, dysregulations occur leading to the onset of diseases. In the development of malignant lymph node diseases, processes can be observed that consistently follow the same pattern. This study aims to define the structural and cellular parameters of the reactive lymph node and to demonstrate how lymph nodes change during tumorigenesis. We analysed benign cases diagnosed as Lymphadenitis (8 patients). Malignant cases with the diagnosis of Nodular Sclerosis classical Hodgkin Lymphoma (5 patients), Mixed Cellularity classical Hodgkin Lymphoma (5 patients), Follicular Lymphoma (7 patients), and diffuse large B-cell Lymphoma (2 patients) were selected. Confocal microscopy was used to visualise immune cells and their compartments in 3D. Based on the fibroblastic reticular cell network we defined five compartments in reactive lymph nodes: Subcapsular sinus, marginal sinus, follicle, T-zone, and medulla. We analysed the cellular composition based on dendritic cells, macrophages, T cells and B cells and extended this analysis to include the presence of extracellular vesicles. During tumorigenesis, the compartmentalisation of the lymph node is progressively destroyed. Despite this ongoing destruction and loss of strict compartmental delineations, at least two distinct structural regions are still visible, defined as follicle-like and T-zone-like compartments. A comparison between reactive and neoplastic cases reveals a progressive cellular and structural homogenisation. Higher masses of CD8 T cells were found under neoplastic conditions and higher masses of CD30 were found in Hodgkin Lymphoma. The volume of CD20 cells in follicles was consistently lower in malignant tissues compared to benign, but higher in T-zones in malignant cases. An increase in vesicles was detected in most neoplasms. These findings offer new insights into cellular and structural remodelling, deepening our understanding of tumorigenesis and paving the way for more precise therapeutic interventions.
Biological patterns of mouse embryonic palatal mesenchymal cells at different palatogenic stages.
Wang Z, Wang S, Zheng X … +7 more , Peng X, Wang X, Zhao X, Wang Y, Chen J, Meng M, Du J
Acta Histochem · 2026 Mar · PMID 41391285 · Publisher ↗
Mouse embryonic palatal mesenchyme (MEPM) cell culture is commonly used to study palate development and cleft palate (CP). However, there are few reports on the changes in the biological patterns of MEPM cells during pal...
Mouse embryonic palatal mesenchyme (MEPM) cell culture is commonly used to study palate development and cleft palate (CP). However, there are few reports on the changes in the biological patterns of MEPM cells during palate development. In this study, we investigated the changes in the biological characteristics of MEPM cells during the critical period of mouse palate development from embryonic day (E) 13.5 to E16.5. First, we examined the proliferation and apoptotic factors, as well as the osteogenic ability, of palatal shelves from E13.5 to E16.5 in vivo using immunohistochemical staining and qRT-PCR. Then we conducted a comprehensive analysis of E13.5-E16.5 MEPM cells and compared their biological characteristics, including cell origin, proliferation, apoptosis, migration, osteogenesis, adipogenesis, and stemness. We found that MEPM cells from E13.5-E16.5 showed positive expression of the mesenchymal marker Vimentin and negative expression of the epithelial marker CK-14. The proliferation of MEPM cells was similar at E13.5 and E14.5, but it gradually declined at E15.5 and E16.5. There was no statistically significant difference in the apoptosis rate among MEPM cells at E13.5-E16.5. The migration ability of MEPM cells gradually decreased from E13.5 to E16.5, and the osteogenic ability of MEPM cells and palate shelves gradually increased. In addition, the expressions of stemness markers gradually decreased, accompanied by a decrease in adipogenic ability. These results indicate differences in the biological characteristics of MEPM cells at different palate development stages, which helps us understand the detailed process of palate development.
Neuronal stress promotes Cre recombinase transfer from oligodendroglia to neurons.
Xu T, Yang K, Feng Y … +5 more , Wu YC, Zhang LY, Yang Z, Yuan F, Lyu H
Acta Histochem · 2026 Mar · PMID 41270366 · Publisher ↗
The study of oligodendrocyte precursor cells (OPCs) in both physiological and pathological contexts is challenging due to their capacity for self-renewal. This research aimed to examine the effects of OPC depletion on ne...
The study of oligodendrocyte precursor cells (OPCs) in both physiological and pathological contexts is challenging due to their capacity for self-renewal. This research aimed to examine the effects of OPC depletion on neurons. Tamoxifen-inducible Sox10/iCreER; netrin-1 (NTN-1 cKO) mice were used to inactivate NTN-1 in Sox10 oligodendroglia at varying tamoxifen doses. The impact of Necrostatin-1s (Nec-1s) and cytarabine on neuronal degeneration was evaluated, along with a comparison of the effects of tamoxifen dissolved in different plant oils on lineage tracing in Sox10/iCreER; tdTomato mice, as well as on neuronal degeneration in NTN-1 cKO mice. Our findings showed that administering 3 mg of tamoxifen per NTN-1 cKO mouse triggered necroptosis and apoptosis in Sox10 cells. Notably, a higher dose of 6 mg of tamoxifen resulted in the degeneration of cortical neurons, which was accompanied by astrogliosis, amyloidosis, and a reduction in microglia. Immunostaining and RNAscope analysis indicated that it was Cre recombinase, rather than Cre mRNA, that was transferred to neurons. Nec-1s and cytarabine successfully prevented cortical neuron degeneration, though through distinct mechanisms. Furthermore, administering tamoxifen dissolved in vitamin E-rich wheat germ oil reduced Cre transfer in both Sox10/iCreER; tdTomato mice and NTN-1 cKO mice, significantly preventing cortical neurons from being labeled with tdTomato and protecting them from degeneration. These results suggest that, under pathological conditions, Cre recombinase can transfer from oligodendroglia to neurons, a process triggered by neuronal stress. This highlights the need for careful consideration in using Cre-loxP lineage tracing and gene-editing methods involving oligodendrocyte lineage cells and neurons.
Distinct roles of lysophosphatidic acid (LPA) receptor signaling in regulating gastric cancer cell functions under chemical versus physiological hypoxia.
Yashiro N, Yamamoto M, Kusumoto Y … +5 more , Nagano S, Tamura M, Shimomura N, Takai M, Tsujiuchi T
Acta Histochem · 2026 Mar · PMID 41265111 · Publisher ↗
Hypoxia plays a crucial role in driving tumor progression by altering cellular signaling pathways. Lysophosphatidic acid (LPA) receptor signaling regulates malignant properties in cancer cells, including motility and che...
Hypoxia plays a crucial role in driving tumor progression by altering cellular signaling pathways. Lysophosphatidic acid (LPA) receptor signaling regulates malignant properties in cancer cells, including motility and chemoresistance. This study aimed to compare the cellular functions of gastric cancer AGS cells under cobalt chloride (CoCl)-induced hypoxia and true hypoxia (1 % O), with a focus on the role of LPA receptor signaling in mediating these responses. Treatment with CoCl (200 μM) elevated LPAR1 and LPAR3 expression while reducing LPAR2 expression, resulting in enhanced cell motility. CoCl also increased AGS cell viability in response to cisplatin (CDDP) in the presence of LPA. These effects were suppressed by LW6, an inhibitor of HIF-1α, indicating HIF-1α involvement. Furthermore, AGS cel motility and CDDP resistance were enhanced by AM966 (LPA antagonist), GRI-977143 (LPA agonist), and (2S)-OMPT (LPA agonist), suggesting that LPA and LPA promote, while LPA suppresses, these cellular functions under CoCl-induced hypoxia. In contrast, under 1 % O conditions, LPAR1 and LPAR3 expression levels were downregulated, while LPAR2 expression remained unchanged. AGS cells cultured at 1 % O showed increased motility but reduced viability in response to CDDP. LW6 further inhibited viability under these conditions. Our results demonstrate that LPA receptor signaling is differentially regulated under CoCl-induced and true hypoxia, contributing to distinct outcomes in cell motility and drug response. This suggests that LPA receptor signaling is a potential target for controlling hypoxia-induced malignant transformation in gastric cancer cells.
S100A8 and S100A9-mediated keratinocyte affecting T lymphocyte immune imbalance through TLR4/NF-κ B in psoriasis.
He Y, Xing J, Li J … +2 more , Zhang K, Li X
Acta Histochem · 2025 Dec · PMID 41252873 · Publisher ↗
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 w...
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.
Immunofluorescent characterization of Klotho and FGF23 in clear cell renal cell carcinoma: A pilot study.
Racetin A, Kelam N, Glavina Durdov M … +1 more , Vukojević K
Acta Histochem · 2025 Dec · PMID 41240794 · Publisher ↗
BACKGROUND/OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of renal malignancy, associated with poor prognosis in advanced stages. Emerging evidence highlights the potential...
BACKGROUND/OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of renal malignancy, associated with poor prognosis in advanced stages. Emerging evidence highlights the potential tumor-suppressive role of the anti-aging protein Klotho (KL) and its cofactor, fibroblast growth factor 23 (FGF23), both of which are implicated in phosphate metabolism and cellular homeostasis. METHODS: Using immunofluorescence and quantitative image analysis, we assessed KL and FGF23 protein levels in 20 ccRCC specimens stratified by tumor grade, alongside adjacent normal tissue. Publicly available RNA-seq and survival data from the TCGA-KIRC cohort were analyzed to complement our findings. RESULTS: Immunofluorescence analysis of 20 ccRCC samples and matched normal tissues revealed consistently low Klotho expression with no significant differences across tumor grades. However, Kaplan-Meier survival analysis revealed that high KL mRNA expression was significantly associated with improved overall survival and disease-free survival, highlighting its role as a protective prognostic biomarker. Multivariate Cox regression confirmed KL as an independent predictor of better overall survival. In contrast, FGF23 protein levels were significantly elevated in ccRCC samples, particularly in high-grade tumors, despite minimal expression in control tissue and no significant differences at the mRNA level in the TCGA cohort. Notably, patients with detectable FGF23 expression had significantly worse survival outcomes, and multivariate analysis identified elevated FGF23 as an independent risk factor for poor prognosis. Age and tumor stage also remain strong prognostic determinants in our models. CONCLUSIONS: These findings suggest a dichotomous role for KL and FGF23 in ccRCC, with KL functioning as a favorable prognostic factor and FGF23 potentially contributing to disease progression and early relapse. Further mechanistic studies are warranted to elucidate their interplay and evaluate their utility as biomarkers or therapeutic targets in renal cancer.
POSTN promotes ferroptosis and contributes to the pathogenesis of IgA nephropathy via GPX4 downregulation.
Jia W, Wu Y
Acta Histochem · 2025 Dec · PMID 41202667 · Publisher ↗
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, w...
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.
Retraction notice to " Paeonol antagonizes oncogenesis of osteosarcoma by inhibiting the function of TLR4/MAPK/NF-?B pathway" [Acta Histochem. 122 (2020) 151455].
Zhou J, Liu Q, Qian R … +3 more , Liu S, Hu W, Liu Z
Acta Histochem · 2025 Dec · PMID 41038745 · Publisher ↗
Abstract loading — click title to view on PubMed.
FoxO1 in skeletal muscle atrophy: Multifaceted regulatory mechanisms and therapeutic opportunities.
Song CY, Zhou TY, Shi HB … +2 more , Li XY, Hong K
Acta Histochem · 2025 Dec · PMID 40992061 · Publisher ↗
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...
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 (FoxO1) 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 FoxO1, such as resveratrol-induced SIRT1 activation and miR-486 mimics, have shown promising results in preclinical models. This review highlights the central role of FoxO1 in molecular pathways, proposes a potential framework for addressing muscle atrophy, and offers new insights into the treatment of sarcopenia and related diseases.
Cancer-associated fibroblast-derived CCL5 enhanced aerobic glycolysis through upregulation of IP3R to promote breast cancer cell metastasis.
Zhang M, Zhu Z, Yang G … +1 more , Zhu Y
Acta Histochem · 2025 Dec · PMID 40992060 · Publisher ↗
BACKGROUND: 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 upregulat...
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: CAF-derived CCL5 enhanced aerobic glycolysis in breast cancer cells by up-regulating IP3R expression, which in turn promoted their metastasis. DATA AVAILABILITY: The data used to support the findings of this study are available from the corresponding author upon request.
Neurochemical heterogeneity of ChAT-immunoreactive neurons in the basal forebrain cholinergic nuclei and striatum in reference to CGRP, CCK, and calcium-binding proteins.
Meher MM, Afrin M, Jahan MR … +4 more , Nozaki K, Masumoto KH, Yanai A, Islam MN
Acta Histochem · 2025 Dec · PMID 40925258 · Publisher ↗
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...
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.
Neuroprotective effect of Urolithin A via downregulating VDAC1-mediated autophagy in Alzheimer's disease.
Zhang B, Zhang X, Treebupachatsakul W … +5 more , Pantan R, Kampan N, Phatsara M, Shi C, Narakornsak S
Acta Histochem · 2025 Dec · PMID 40897157 · Publisher ↗
BACKGROUND: 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 ac...
BACKGROUND: 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-injured N2a and PC12 cells. METHODS: 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-injured cells. RESULTS: 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-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-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. CONCLUSION: 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.
Blood transfusion mediated tumor microenvironment remodeling in breast cancer.
Yin Q, Zhang S, Ouchari M … +11 more , Wang P, Zhao A, Zeng L, Wang J, Yao K, Tang S, Ma H, Girondin AC, Yang H, Zheng X, Qu Z
Acta Histochem · 2025 Dec · PMID 40849961 · Publisher ↗
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 adversel...
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.
Corrigendum to "Inducible gankyrin overexpression drives hepatocarcinogenesis in a liver-specific zebrafish model" [Acta Histochem. 127 (2025) 152280].
Sun Y, Gong Z, Lin YM … +1 more , Lu JW
Acta Histochem · 2025 Dec · PMID 40829969 · Publisher ↗
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Advancing triple-negative breast cancer therapy: 3D in vitro models to unravel drug resistance mechanisms and tumor microenvironment interactions.
Baskar G, Palaniyandi T
Acta Histochem · 2025 Dec · PMID 40819389 · Publisher ↗
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 ani...
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 in vivo 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.
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