Histology and histopathology最新文献

Background: This study tested the hypothesis that PI3K/Akt/GSK3β and TGF-β/Smad2/3 signaling play essential roles in mediating the epithelial-mesenchymal transition (EMT) and fibrosis, resulting in the deterioration of renal function and parenchyma in chronic kidney disease (CKD) rats, which is reversed by early empagliflozin treatment.

Methods and results: NRK-52E cells were divided into the A1 (NRK-52E), A2 (NRK-52E + 200 μM p-Cresol), A3 (NRK-52E + 200 μM p-Cresol + 50 μM empagliflozin), B1 (NRK-52E), B2 (NRK-52E + 5 ng/mL TGF-β1) and B3 (NRK-52E + 5 ng/mL TGF-β1 + 50 μM empagliflozin) groups. Compared with those in the A1 group, the expression levels of proteins related to the EMT (TGF-β1/p-Smad2/p-Smad3/α-SMA), extracellular matrix (MMP2/9) and EMT (IGF-1) activators were significantly higher in the A2 group, but these changes were significantly reversed in the A3 group, whereas the protein expression levels of antifibrotic markers (TIMP1/TIMP2) exhibited the opposite pattern to the EMT-related proteins among the groups (all p<0.001). The expression of these proteins, along with the other EMT markers (snail, fibronectin, and vimentin) related to cellular function/protein expression, also exhibited an identical pattern to the A1 to A3 groups among Groups B1 to B3 (all p<0.001). Adult male SD rats were categorized into Groups 1 (sham-operated control), 2 (CKD) and 3 (CKD + empagliflozin). On Day 56 after CKD induction, the renal artery resistive index (RARI) was significantly higher in Group 2 than in Groups 1 and 3 and significantly higher in Group 3 than in Group 1 (all p<0.0001). The expression of EMT (Snail/α-SMA/fibronectin/vimentin/TGF-β1/p-Smad2/3), apoptotic (cleaved caspase-3/cleaved-PARP), inflammatory (HIF-1α/IL-1β/TNF-α/MPO/MMP-2/MMP-9), and cell stress signaling (p-PI3K/p-Akt/GSK-3β) proteins and the cellular kidney injury score, expression of fibrosis and EMT markers (Snail/vimentin)/glomerular-hypercellularity/fibrocellular crescent formation displayed an identical pattern, whereas the cellular expression of podocyte components (podocin/synaptopodin/ZO-1) displayed the opposite pattern to the RARIs among the groups (all p<0.0001).

Conclusions: Empagliflozin protected kidney function and architecture mainly by suppressing fibrosis, cellular oxidative stress signaling, the EMT and inflammation.

Microtubule-associated protein tau is predominantly expressed in neurons in the form of multiple isoforms generated by alternative splicing. These isoforms differ in the presence of either three or four microtubule-binding repeats. These binding regions not only regulate tau's interaction with microtubules but are also critically involved in its pathological self-aggregation. Such aggregates are a defining feature of a group of neurodegenerative disorders collectively referred to as tauopathies. In this work, we examine the mechanisms underlying tau self-aggregation, the molecular and cellular factors that drive this process, and the structural features of tau aggregates. Aggregates composed of isoforms with three versus four microtubule-binding repeats display distinct morphologies, which serve as pathological hallmarks for different tauopathies. Finally, we discuss potential therapeutic strategies aimed at preventing or promoting the clearance of tau aggregates.

Recently, the role of macrophages in tendon repair has received increased attention. These cells are versatile, playing multiple roles, such as defending the host, engulfing debris, producing growth factors, and releasing substances that can both promote and alleviate inflammation. Within the scope of tendon repair and tendinopathy resolution, macrophages are essential contributors. However, the current understanding of macrophage involvement in tendon healing remains limited. Hence, understanding macrophages' impact on tendon healing is of considerable importance for devising innovative treatment approaches. It is crucial to examine the precise role that macrophages play in tendon recovery, as it provides new understanding that can propel both research and the development of therapeutic methods aimed at enhancing tendon recovery moving forward.

Aims: The hippocampal region is an essential area for memory. Alzheimer's disease (AD) continues to impact this brain region. It is caused by the accumulation of amyloid-β (Aβ) along with neurofibrillary tangles, together with glial fibrillary acidic protein (GFAP) expression, which causes loss of synapses, resulting in memory problems. Consuming a high-fat diet (HFD) causes the abnormal production of certain neurotransmitters through the gut-brain axis system, resulting in hippocampal neuron damage. Therefore, this study examined the effects of polysaccharides from Schizophyllum commune (Fr.) or split-gill mushroom (SG) in rats induced with an HFD.

Methods: The Y-maze test assessed spontaneous alternation percentages and short-term memory in all rat groups, while H&E and Cresyl violet staining revealed alterations in the characteristics of neurons across treatment groups. Immunofluorescence was employed to identify the expressions of neurodegenerative and inflammatory proteins.

Results: The short-term memory was evaluated using the Y-maze test, which found that the spontaneous alternation percentage was lower in the HFD group and higher in the HFD+SG group compared with the control group. Alterations in neuron characteristics were revealed by Cresyl violet and H&E staining. The HFD group was found to have necrotic neurons; however, the HFD+SG group had less damage than the HFD group. Immunofluorescence observations indicated the expression of Aβ and GFAP proteins; the HFD group showed an increase in Aβ and GFAP accumulation, whereas in the HFD+SG group, these were significantly reduced.

Conclusions: The study demonstrated improvements in hippocampal neurons, suggesting that polysaccharides from SG may be able to lessen the harm caused to the brain by consuming an HFD.

Neuronal nuclei (NeuN), also known as Rbfox3, is a widely used neuronal marker for identifying postmitotic neurons in both basic neuroscience and diagnostic neuropathology. Since its discovery, NeuN immunoreactivity has enabled accurate neuron counting, injury assessment, and anatomical mapping. However, accumulating evidence demonstrates that NeuN is not universally expressed across all mature neurons. Specific neuron types, such as olfactory mitral cells, cerebellar Purkinje cells, and retinal photoreceptors, consistently lack NeuN immunostaining despite functional maturity. Moreover, NeuN expression is dynamically regulated under pathological conditions. In ischemia-reperfusion (I/R) injury, neurodegenerative diseases (e.g., Alzheimer's and Parkinson's), and traumatic brain injury or epilepsy-selected for their representative diversity in pathophysiological stress (ischemic, degenerative, and mechanical)-NeuN downregulation may reflect functional compromise, stress responses, or reversible transcriptional changes rather than irreversible cell loss. These findings highlight the limitations of interpreting NeuN negativity as neuronal death. This review synthesizes recent findings on NeuN expression patterns, molecular mechanisms regulating its presence or absence, and the implications for research and diagnosis. We propose that NeuN should not be regarded as a binary marker but rather as a dynamic indicator of neuronal state. Multi-marker strategies and molecular tools such as spatial transcriptomics and RNA sequencing are suggested to improve the resolution of neuronal analysis. As histological and transcriptomic approaches converge, NeuN's role will likely expand from a structural identifier to a contextual readout of neuronal integrity and function.

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.

Background: Cantharidic acid (CA) is a cantharidin analog and has antitumor effects. This study aimed to investigate the antitumor activity of CA against colorectal cancer (CRC) and the underlying mechanisms of this activity.

Methods: The impact of CA on the viability of the normal FHC cell line was evaluated by the CCK-8 assay. The malignant behavior of CRC cells was determined using the CCK-8 assay, colony formation assay, Transwell assay, and an LDH commercial kit. The surviving and apoptotic cell numbers were examined via flow cytometry and calcein-AM/PI staining. The ultrastructure of the mitochondria was observed, and the concentration of mtDNA was detected via RT-qPCR. A subcutaneous xenograft tumor model in nude mice was established, and pathological staining was used to assess apoptosis and changes in protein expression. Western blotting was used to evaluate the levels of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/glutathione peroxidase 4 (GPX4) pathway-related proteins and mitochondrial damage-related proteins.

Results: CA did not significantly affect FHC viability but was able to reduce CRC cell viability, decrease colony-forming ability, inhibit migration and invasion, and induce apoptosis. CA treatment disrupted mitochondrial morphology and structure and caused a decrease in mitochondrial membrane potential, ATP production, and mtDNA concentration. Treatment with Mito-TEMPO (a mitochondrion-targeted antioxidant) reversed the effects of CA treatment on the above metrics. Furthermore, CA blocked the Nrf2/HO-1/GPX4 pathway, whereas the Nrf2 agonist TBHQ alleviated CA-induced mitochondrial dysfunction. CA treatment decreased the volume and mass of tumor tissue, inhibited cell proliferation, and promoted apoptosis. Notably, CA also led to mitochondrial dysfunction in vivo, which was effectively mitigated by TBHQ.

Conclusion: CA blocks the Nrf2/HO-1/GPX4 pathway, causing mitochondrial dysfunction and apoptosis, and thus inhibits the malignant progression of CRC. CA has potential as a therapeutic agent for CRC.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive peripheral T-cell lymphoma with a poor prognosis. Lymphomatous serous effusion, defined as the presence of malignant lymphoma cells in the pleural, pericardial, or peritoneal fluid, is a rare but clinically important manifestation, particularly when a lymph node biopsy is difficult or delayed. We performed a narrative review of case reports and a small series of AITL cases with lymphomatous effusion, focusing on the clinical presentation, cytologic features, ancillary studies, and outcomes. Reported patients are typically older adults with advanced-stage disease; effusions are usually exudative, of low volume, and cytologically tumor-cell-poor but inflammation-rich; therefore, atypical T follicular helper (TFH)-type T cells are easily overlooked or misclassified. Immunocytochemistry (ICC) on cell block or cell-transfer preparations, flow cytometry, and EBER in situ hybridization improve the recognition of the AITL phenotype, whereas next-generation sequencing (NGS) can detect hallmark mutations such as RHOA G17V, TET2, DNMT3A, and IDH2 directly from effusion samples, enabling a less invasive diagnostic approach when tissue is not readily available. According to previous reports, lymphomatous effusion, which is frequently measured in months, is associated with a short survival. Based on these data and current World Health Organization (WHO) and National Comprehensive Cancer Network (NCCN) guidance, we propose a practical fluid-based diagnostic algorithm that integrates cytology, ancillary tools, and lymph node biopsy when feasible, and we highlight the need for standardized effusion-based workflows, multicenter registries, and the integration of liquid biopsies, multiomics, and artificial intelligence-assisted cytology to refine risk stratification and guide therapy in this distinct subgroup.

Oxygen is an essential element in the process of cellular oxidation, and hypoxia, a state of insufficient oxygen, can profoundly influence cellular adaptive responses through gene transcription, thereby impacting cell metabolism, angiogenesis, and inflammation. Hypoxia-inducible factor (HIF), particularly its alpha subunit (HIF-1α), is a critical transcription factor that orchestrates cellular adaptation to hypoxic environments and plays a multifaceted role in various cellular activities. In recent years, HIF-1α has been widely implicated in stimulating hematopoietic function and the good effect of roxadustat in treating renal anemia. However, the specific role of HIF-1α in bone metabolism remains unclear. More and more studies have shown that HIF-1α can not only directly affect osteoblasts, osteoclasts, osteocytes, and bone matrix during bone remodeling, but also locally and remotely regulate macrophages and various cytokines involved in bone remodeling. In addition, HIF-1α can indirectly regulate bone metabolism by promoting angiogenesis and regulating cell metabolism. This review comprehensively elucidates the intricate mechanisms by which HIF-1α influences bone metabolism. The aim is to provide a robust theoretical foundation for exploring the potential therapeutic application of roxadustat to improve bone metabolism in patients with Chronic Kidney Disease-related Osteoporosis (CKD-RO). It is important to note that, while this review highlights promising findings, the current evidence is primarily derived from preclinical animal studies and necessitates rigorous clinical validation.

LONP1, a mitochondrial ATP-dependent protease, plays a crucial role in mitochondrial homeostasis by regulating protein turnover and mitophagy. Recent studies have highlighted its upregulation in various cancers, including colorectal cancer (CRC). This study investigates the expression of LONP1 in colon adenocarcinoma (COAD) and its correlation with mitophagy-related proteins and immune infiltration markers. Using publicly available databases and immunohistochemical analysis of 50 COAD patient samples, we confirmed that LONP1 expression is significantly elevated in COAD compared with normal tissue. High LONP1 levels were associated with tumor progression, TP53 mutation status, and poor prognosis. Correlation analyses revealed that LONP1 is closely linked to mitochondrial dynamics, mitophagy regulators (PINK1, AMBRA1, FUNDC1), and metabolic reprogramming. Additionally, LONP1 expression positively correlated with tumor-infiltrating lymphocytes, particularly CD8+ T cells, suggesting a potential role in immune evasion. Immunohistochemical analysis distinguished two patterns: high LONP1/low TOMM20 expression associated with aggressive tumors and low LONP1/high TOMM20 expression linked to better outcomes and stronger immune infiltration. These findings suggest that LONP1 contributes to tumor progression through mitochondrial regulation and immune modulation, highlighting its potential as both a prognostic biomarker and a therapeutic target in COAD.