In our recent study, we identified Rab10-positive long tubular endosomes, which originate from macropinocytic cups, as a novel endocytic pathway in RAW264 cells. This pathway is unique because it bypasses the lysosomal degradation route and proceeds toward the Golgi region, distinguishing it from previously known endocytic routes. However, its function remains entirely unknown. Upon exploring the cargo transported by Rab10-positive tubular endosomes, we discovered that PD-L1, a cancer immune checkpoint molecule expressed on cancer cells and macrophage surfaces, was abundantly localized in Rab10-positive tubular structures in RAW264 cells. This suggests that PD-L1 may be a significant cargo for these endosomes in macrophages. These findings offer new insights into the role of Rab10-positive tubular endosomes in the intracellular transport of PD-L1, potentially influencing its expression on the cell surface.

Eribulin, a microtubule inhibitor, is effective as later-line therapy for metastatic breast cancer (MBC) and has been reported to remodel the tumor microenvironment and inhibit epithelial-mesenchymal transition (EMT). However, the association between pretreatment EMT status and eribulin efficacy remains unclear. We retrospectively analyzed 41 patients with MBC (excluding invasive lobular carcinoma) treated with eribulin between 2013 and 2020. Formalin-fixed, paraffin-embedded biopsy specimens were examined by immunohistochemistry (IHC) using anti-E-cadherin (24E10) and anti-vimentin (V9) antibodies. Complete membranous E-cadherin expression (3+) was defined as normal; reduced expression (2+, 1+, 0) as altered. Negative vimentin was considered normal; positive expression, altered. Co-localization of E-cadherin and vimentin was assessed by multi-immunofluorescent staining. Of the 41 patients, 24 responded to eribulin and 17 did not. Progression-free survival (PFS) and overall survival (OS) were significantly longer in responders than in nonresponders ( < 0.001 and = 0.0044). Altered E-cadherin and/or vimentin expression was more frequently observed in responders ( = 0.013) and associated with longer progression-free survival ( = 0.048). These results suggest that eribulin efficacy may be predicted by altered E-cadherin and vimentin expression before treatment.

Secondary hyperparathyroidism (SHPT) associated with chronic kidney disease (CKD) is characterized by parathyroid hyperplasia, which progresses from diffuse-type to nodular-type lesions. Nodular hyperplasia in SHPT is often considered to exhibit monoclonal proliferation, suggesting a shift toward neoplastic behavior, but the molecular mechanisms underlying this transformation remain poorly defined. In this study, we analyzed 340 surgically resected parathyroid glands from long-term dialysis patients who met clinical indications for parathyroidectomy. Based on histological architecture, lesions were classified into diffuse, nodular, or diffuse-nodular (mixed) hyperplasia. We conducted immunohistochemical analysis of Ki-67 and p16 (CDKN2A), and further assessed region-specific DNA methylation of the p16 promoter using a bisulfite padlock probe method combined with rolling circle amplification. Nodular-type lesions exhibited significantly higher Ki-67 indices and lower p16 expression compared to diffuse-type lesions. methylation analysis revealed increased methylation of the p16 promoter specifically in nodular regions, suggesting epigenetic silencing. Our findings suggest that p16 silencing through promoter methylation may play a critical role in the clonal expansion and histopathological transformation of parathyroid tissue in SHPT. These results underscore the importance of epigenetic regulation in SHPT progression and suggest that p16 methylation could represent a potential biomarker for nodular transformation. The padlock probe-based detection system enabled high-resolution spatial analysis of methylation patterns and may serve as a valuable tool for dissecting epigenetic events in early phase of cellular alterations.

Prostate cancer is one of the most common malignancies in men and remodeling of extracellular collagen, especially collagen type I immensely contributes to the progress of prostate cancer. Discoidin domain receptor 2 (DDR2) is a receptor of collagen type I and transmits intracellular signaling in not only normal cells but also malignant cells, facilitating tumor progression. However, clinical and biological significance of DDR2 has not been well examined in prostate cancer. We therefore immunolocalized DDR2 and collagen type I in 117 prostate carcinoma tissues and correlated their immunoreactivity with clinicopathological characteristics of prostate cancer. We also conducted experiments using human prostate cancer cell lines to confirm the findings from immunohistochemical study. DDR2 immunoreactivity was positively associated with an aggressive phenotype of prostate cancer, partially in association with dense collagen I tissues which consisted of thin fibers. In addition, DDR2 immunoreactivity was significantly correlated with adverse clinical outcomes of prostate cancer. experiments revealed that DDR2 promoted proliferation and migration of PC-3 and DU-145 prostate cancer cell lines. It is therefore speculated that DDR2 promoted prostate cancer progression by interacting with collagen I, serving as a potent prognostic factor in prostate cancer.

Sex-determining region Y () triggers testis development in mammals, and the presence or absence of testicular secretion determines their sex-specific brain phenotype. Mice with Y chromosome replaced by that of (Y ) frequently display sex reversal due to delayed expression. However, brain sexual dimorphism under conditions of disorders of sex development remains unclear. Here, we report sex differences in the sexually dimorphic nucleus of the preoptic area, delineated by cells positive for calbindin D28k, a male-predominant neuronal marker (CALB-SDN), in Y mice. The mice were divided into females and males according to gonadal phenotype. Cells immunoreactive (ir) for calbindin D28k (CALB) were more extensively distributed in male Y mice, compared with females. The CALB-ir cell numbers in the CALB-SDN were significantly higher in Y males than in Y females, which had numbers comparable to wild type females. No left-right differences in CALB-ir cell numbers were observed in the CALB-SDN. Collectively, these results demonstrate that sexual dimorphism of the CALB-ir cell cluster in the CALB-SDN strongly correlates with the gonadal sex phenotype rather than with the chromosomal sex in the Y mice, suggesting the effect of testicular secretion on the brain sexual differentiation with aberrant Y-linked gene expression.

This study assessed the effectiveness of a combination of platelet-rich plasma (PRP) and β-tricalcium phosphate/polylactic-co-glycolic acid (β-TCP/PLGA) fibers in the treatment of osteoporotic vertebral defects in rats. Seventy-two female Sprague-Dawley rats subjected to ovariectomy to induce osteoporosis were divided into three groups to receive different treatments for critical bone defects created in the lumbar vertebrae. The PRP group received β-TCP/PLGA fibers infused with PRP, the control group received no material, and the other group received the same fibers infused with phosphate-buffered saline (PBS). Over a period of 12 weeks, bone regeneration, macrophage differentiation, and inflammatory responses were evaluated histologically. Compared to the PBS group, the PRP-treated group demonstrated significantly enhanced early stage bone formation, increased expression of osteogenic markers, and a favorable shift in macrophage activity from the M1 inflammatory phenotype to the M2 healing phenotype. These outcomes suggest that the combination of PRP and β-TCP/PLGA fibers not only effectively promotes bone repair under osteoporotic conditions but also modulates the immune response to facilitate better healing, indicating its potential as a beneficial surgical intervention for osteoporotic vertebral fractures.

The long non-coding RNA reportedly forms a circular RNA variant (circ). As circ is expressed in various cancers and has been implicated in promoting cancer cell proliferation and tumor progression, it is considered a potential biomarker and therapeutic target. We previously confirmed that circ expression varies according to the Gleason pattern, a morphological indicator of malignancy in prostate cancer. In this study, we assessed the expression of circ using BaseScope assay with prostate cancer tissues and evaluated the correlation with the Grade Group (based on Gleason pattern), an indicator used to morphologically evaluate the degree of malignancy of prostate cancer. The relationship between circ expression and tumor proliferation was evaluated using cells in which circ expression was suppressed using the clustered regularly interspaced short palindromic repeats (CRISPR)/RfxCas13d system. BaseScope assay confirmed that circ expression was significantly higher in Grade Group 2-5 (intermediate- and high-grade groups) than Grade Group 1 (low-grade group). experiments using the CRISPR/RfxCas13d system showed that specific suppression of circ expression resulted in a significant reduction in the number of prostate cancer cells. The results of this study suggest that circ is involved in tumor growth in prostate cancer and may serve as a therapeutic target for moderately and highly malignant prostate cancers that express circ.

-linked -acetylglucosamine (-GlcNAc) modification, known as -GlcNAcylation, is a dynamic post-translational modification involving the addition of -acetylglucosamine to serine or threonine residues. It has emerged as a critical regulator in diabetic pathophysiology. This review summarizes current research on the role of -GlcNAcylation in hyperglycemia-induced cellular dysfunction, and focuses on vascular smooth muscle cells, renal cytoskeletal proteins, and diabetic complications in animal and human models. Studies reveal that hyperglycemia upregulates -GlcNAc transferase activity, disrupting the interplay between glycosylation and phosphorylation, thereby impairing signaling pathways and exacerbating vascular proliferation and renal cytoskeletal disorganization. Notable findings include the imbalance of -actin modifications in diabetic nephropathy, correlated with podocyte damage and glomerular abnormalities. By elucidating these mechanistic pathways, this review underscores the potential of -GlcNAcylation as a biomarker and a therapeutic target. Future research should focus on tissue-specific effects and pharmacological strategies that mitigate diabetes-induced complications while preserving normal cellular functions.

α-Synuclein is the causative gene for and (heterozygous triplication of ) and is associated with Parkinson's disease, where it localizes to presynaptic terminals in mature neurons. Beyond Parkinson's disease, α-synuclein has also been implicated in various other neuronal disorders. studies using purified α-synuclein protein have suggested it is involved in synaptic vesicle assembly. However, its physiological function and the ultrastructure of its localization sites in presynaptic terminals remain unclear. To address this, we generated transgenic mice overexpressing human α-synuclein tagged with mKate2 (hSNCA-mKate2 mice) to investigate its role in synaptic vesicle pool formation at presynaptic terminals. These mice showed normal growth and fertility, and even at 1-yr. old, they showed no motor dysfunction compared to their wild-type littermates. Additionally, no abnormal protein aggregates indicative of neurodegeneration were observed. In this review, we summarize recent findings on the role of α-synuclein within presynaptic terminals, utilizing hSNCA-mKate2 mice in combination with in-resin correlative light and electron microscopy, electron microscopy, and immunohistochemistry.

In the field of histochemistry and cytochemistry (histocytochemistry), fixation is a critical process for preserving biological structures and enabling accurate analysis. Fixation methods, broadly categorized into precipitating and cross-linking techniques, stabilize biomolecules such as proteins, sugars (carbohydrates) and nucleic acids, although lipids often require specific handling due to the loss during a routine procedure. Traditional staining methods have evolved into advanced techniques like immunohistochemistry (IHC) and hybridization (ISH), which allow for precise analysis of the expression of specific molecules. IHC employs antibodies to visualize specific antigens, with fixation playing a vital role in maintaining antigen integrity. However, excessive fixation can mask epitopes, requiring antigen retrieval techniques to restore antigenicity. Microwave-induced retrieval, for instance, enhances staining efficacy while introducing further fixation by promoting molecular interactions. ISH, which targets nucleic acids with specific base sequences, is also sensitive to fixation conditions. Formaldehyde-based fixatives react variably with purines and pyrimidines, affecting hybridization efficiency with a probe. Positive controls like 28S rRNA help to standardize ISH across facilities, ensuring reproducible and reliable results. Variability in fixation protocols among institutions brings fatal defects in achieving consistent results. Shared standards or the use of robust controls can alleviate these issues, enhancing the accuracy and reliability of histocytochemical analyses for both research and clinical applications.

SNX25 is a member of the sorting nexin (SNX) superfamily, which plays crucial roles in membrane trafficking, cell signaling, and organelle dynamics. Our research has focused extensively on SNX25, demonstrating that SNX25-positive macrophages participate in inflammatory responses and pain perception through various signaling pathways. Atherosclerosis is now widely recognized as a chronic inflammatory disease of the vasculature, with macrophages serving as central contributors to its progression. These macrophages accumulate after internalizing oxidized low-density lipoproteins (oxLDL), transforming into foam cells that elicit inflammatory responses and promote atherosclerotic progression. To explore the impact of SNX25 on atherosclerosis, we induced the condition in apolipoprotein E-deficient (APOE) mice using a high-fat diet. As expected, SNX25 expression was observed in macrophages within atherosclerotic plaques. In SNX25 mice on an APOE genetic background, plaque size was significantly smaller than in their SNX25 counterparts. Furthermore, bone marrow transplantation from SNX25 mice into APOE recipients resulted in a marked reduction in foam cell formation and accumulation compared to transplants from SNX25 donors. These histopathological findings suggest that SNX25 may regulate macrophage activity under pathological conditions, identifying a novel role for SNX25 in the pathogenesis of atherosclerosis.

Squamous cell carcinoma (SCC), a common malignancy affecting the skin, vagina, uterine cervix, anus, larynx, and upper digestive tract, is characterized by significant disruption of cell-cell adhesion in stratified squamous epithelium during tumorigenesis, progression, and metastasis. CALML5, a stratified epithelial-specific protein linked to desmosomal junctions, plays a key role in cell adhesion and is notably downregulated in human papillomavirus (HPV)-associated cervical SCC. Esophageal and pharyngeal cancers, commonly with a squamous cell phenotype, have distinct etiologies: oropharyngeal carcinoma is strongly associated with HPV, whereas esophageal carcinoma is linked to environmental factors such as smoking, alcohol, and diet. To investigate the role of CALML5 in these cancers, we performed immunohistochemical analyses on clinical samples and explored its regulatory mechanisms using studies with human esophageal SCC cell lines. Our findings revealed that CALML5 expression is suppressed in early-stage esophageal SCC but reactivated at invasive sites in well to moderately differentiated SCC undergoing keratinization. In specialized SCC with sarcomatoid component, CALML5 reactivation occurred alongside aberrant KLF4 expression, highlighting its context-dependent role in tumor progression. Conversely, while HPV-unrelated oropharyngeal SCC exhibited patterns similar to esophageal SCC, HPV-related oropharyngeal SCC consistently showed suppressed CALML5 expression due to impaired KLF4 nuclear translocation. These results suggest that CALML5 functions as a tumor suppressor in HPV-associated cervical SCC but may be reactivated in non-HPV-associated invasive SCC, emphasizing its complex role in SCC pathogenesis and the need for careful interpretation of its expression in clinical contexts.

Ibrutinib is an oral irreversible Bruton's tyrosine kinase (BTK) inhibitor that blocks BTK activity by forming covalent bonds with the thiol group of cysteine in the ATP-binding pocket via Michael addition. However, it also reacts with a variety of off-target nonspecific proteins. In this study, we attempted to generate a specific antibody against ibrutinib and develop an immunohistochemical method to detect the ibrutinib-protein conjugates. Ibrutinib has the same amino group as the nucleobase adenine. Paraformaldehyde fixation could not fix it to the tissue via this amino group. However, ibrutinib covalently binds to proteins such as BTKs to exert its action and is therefore immobilized in tissue as ibrutinib-protein conjugates. Thus, immunohistochemistry for ibrutinib detects the location of the ibrutinib-protein conjugates, that is, the sites of covalently bound to the tissue via Michael addition. Using this immunohistochemical method, we visualized the ibrutinib-protein conjugates in the rat gastrointestinal tract (gastric body, duodenum, jejunum, ileum, and colon). This study is the first to elucidate the location of the ibrutinib-protein conjugates in the rat gastrointestinal tract and helps to clarify the mechanism of ibrutinib-induced toxicity.

Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is critical for determining treatment strategies for patients with pancreatic cancer. However, conventional pathological examination using hematoxylin and eosin (H&E) staining is time-consuming. Microscopy with ultraviolet surface excitation (MUSE) enables rapid pathological diagnosis without requiring slide preparation. This study explores the potential of combining MUSE imaging with a cycle-consistent generative adversarial network (CycleGAN), an image generation algorithm capable of learning translations without paired images, to enhance diagnostic workflows for pancreatic EUS-FNA/B. Thirty-five pancreatic specimens were stained with Terbium/Hoechst 33342, and deep ultraviolet (DUV) fluorescence images were captured by exciting the tissue surface. These fluorescence images, along with H&E-stained formalin-fixed, paraffin-embedded (FFPE) sections from the same specimens, were divided into 256 × 256-pixel segments for CycleGAN training. The algorithm was employed to translate pseudo-H&E images from MUSE test images. The pseudo-H&E images generated by the CycleGAN showed improved inter-pathologist agreement among three pathologists compared with the original MUSE images. We established a technique to perform MUSE imaging on small pancreatic samples obtained through EUS-FNA/B and confirmed that H&E-style translation using CycleGAN simplified interpretation for pathologists. Integrating MUSE imaging with CycleGAN has the potential to offer a rapid, cost-effective, and accurate diagnostic tool.

Gastric cancer (GC), particularly the undifferentiated type, is frequently associated with peritoneal metastasis, which significantly worsens prognosis due to its resistance to conventional treatments. Photodynamic therapy (PDT) is localized treatment using a photosensitizer (PS) activated by light of a specific wavelength to generate cytotoxic reactive oxygen species that induce cell death. Severe adverse events were reported from clinical trials investigating PDT for peritoneal dissemination conducted until the early 2000s, leaving its safety and clinical effectiveness unestablished. The present study explored whether "non-cytotoxic" PDT using talaporfin sodium (TS) could enhance efficacy of chemotherapeutic agents in undifferentiated GC cell line HGC27. Cell viability was evaluated with MTT assay following TS-PDT, and the synergistic effect between non-cytotoxic TS-PDT and anticancer drug SN-38 was assessed. Changes in expression of drug resistance markers were analyzed through qRT-PCR, Western blotting, and immunocytochemistry. We found that non-cytotoxic TS-PDT enhanced the efficacy of chemotherapy in the undifferentiated GC cell line and reduced the expression of C-X-C chemokine receptor type 4, a key marker associated with GC stem-like properties. These findings highlight the potential of non-cytotoxic TS-PDT as a synergistic treatment approach. We conclude that non-cytotoxic TS-PDT could enhance drug sensitivity and offers a promising therapeutic strategy for GC.

Conventional histopathological techniques, such as hematoxylin and eosin staining, are limited to 4-5 μm-thick tissue sections, restricting visualization to two-dimensional planes. Moreover, acquisition of three-dimensional horizontal images from the skin surface remains challenging, hindering precise assessment of tumor margins in skin lesions. This challenge is particularly pronounced in extramammary Paget's disease (EMPD), in which diffuse epidermal tumor cell spread complicates accurate evaluation of lesion extent. We hypothesized that combining horizontal sectioning with identification of individual tumor cells would enhance the determination of surgical margins. In this study, we developed a deep-imaging technique utilizing fluorescent solvatochromic dyes (LipiORDER and HistoBright) and two-photon microscopy to achieve high-resolution tumor margin visualization in EMPD. This technique enables identification of tumor cells in frozen and paraffin-embedded tissue blocks, as well as in live skin tissue under physiological conditions. Our novel approach holds substantial promise for improving the precision of surgical-margin assessment in EMPD and other cutaneous malignancies.

Immune tolerance is essential for safeguarding the body's own tissues from immune system attacks. During pregnancy, the maternal immune system tolerates the semi-allogeneic fetus through mechanisms such as placental programmed cell death 1 (PD-1)-ligand 1 (PD-L1) expression, regulatory T cells (Tregs), cytokine modulation, and hormonal changes. Placental PD-L1 is particularly important in suppressing maternal immune responses and preventing fetal rejection. Following delivery, the loss of the PD-L1-rich placenta can destabilize immune tolerance, potentially leading to postpartum autoimmune diseases such as fulminant type 1 diabetes, characterized by rapid insulin depletion and severe hyperglycemia. Similarly, immune checkpoint inhibitors (ICIs), widely used in cancer immunotherapy, block immune checkpoints like PD-1 and PD-L1 to enhance antitumor immunity by disrupting immunotolerance to tumors. However, this mechanism can sometimes result in immune-related adverse events (irAEs), including fulminant type 1 diabetes. Given the critical role of HLA haplotypes and environmental factors in the development of autoimmune conditions, identifying shared factors among postpartum individuals and patients undergoing ICI therapy who experience immune system abnormalities could provide valuable insights. Such understanding may improve strategies for managing autoimmune diseases associated with both postpartum immune changes and ICI treatments.

SET domain bifurcated 1 (SETDB1), a histone H3K9-specific methyltransferase, is crucial for heterochromatin formation and intestinal homeostasis, but its role in intestinal ischemia-reperfusion injury (IRI) remains unclear. This study investigated changes in SETDB1-mediated nuclear chromatin regulation in intestinal epithelial cells (IECs) using an IRI mouse model. Jejunal samples were collected after 75 min of ischemia followed by 24 hr of reperfusion. Sinefungin was administered as a histone methyltransferase inhibitor. Morphologic changes were evaluated using hematoxylin-eosin staining and electron microscopy, and cell-adhesion molecule expression, including ZO-1, E-cadherin, integrin-β4, and laminin, was evaluated using immunohistochemistry. Super-resolution microscopy analyzed intranuclear SETDB1 localization and heterochromatin formation in IECs. IRI-affected jejunum exhibited massive IEC detachment, dilated intercellular spaces, basement membrane damage, and decreased expression of E-cadherin and integrin-β4. Sinefungin prevented these changes, however. The proportion of IECs expressing nuclear SETDB1 throughout the euchromatin was significantly higher in IRI-affected jejunum (77.8%) than sham-treated (3.0%) or sinefungin-treated, IRI-affected jejunum (2.7%). The proportion of IECs with decreased heterochromatin was significantly higher in sinefungin-treated, IRI-affected jejunum (84.3%) than untreated IRI-affected jejunum (15.6%). These findings suggest that SETDB1-mediated chromatin regulation is pivotal in intestinal IRI and represents a potential therapeutic target.

Spinal cord injury (SCI) is incurable and often leads to permanent motor dysfunction, paralysis, and sensory impairment. We previously developed a method to directly reprogram human fibroblasts into neuron-like cells using only chemical compounds. In a rat model of SCI, we transplanted chemically reprogrammed cells, termed immature chemical-induced neuron-like (CiN) cells, derived using the developed method with slight modifications and found that the immature CiN cells exhibited therapeutic efficacy in SCI. As primate models more closely mimic humans than rat models, primate experiments are required to more accurately assess the safety and efficacy of immature CiN cells before their use in humans. Therefore, in this study, we aimed to determine the therapeutic efficacy of immature CiN cell transplantation in a marmoset SCI model. Immature CiN cells were transplanted into a subacute marmoset model of SCI on Day 9 after contusion injury, and the therapeutic efficacy was assessed. Motor recovery after SCI was assessed based on spontaneous motor activity and the original open-field rating scale over six weeks, after which the spinal cord at the injury site was subjected to histopathological and MRI analyses. Animals transplanted with immature CiN cells exhibited significantly enhanced motor recovery compared to control animals, consistent with improved nerve recovery or preservation. Our findings suggest that immature CiN cells can effectively treat SCI in primates.

Cell-to-cell communications are desirable for efficient functioning in endocrine cells. Gap junctions and paracrine factors are major mechanisms by which neighboring endocrine cells communicate with each other. The current experiment was undertaken to morphologically examine gap junction expression and developmental changes in rat adrenal medullary chromaffin (AMC) cells. The expression of connexin 43 (Cx43) was conspicuous in the rat adrenal cortex, but not detected immunohistochemically in neonatal or adult AMC cells. Consistent with the morphological findings, the phosphorylated and non-phosphorylated forms of Cx43 were predominantly and faintly detected by immunoblotting in the adrenal cortical and medullary homogenates, respectively. In contrast to Cx43, Cx36-like immunoreactive (IR) material was detected in neonatal AMC cells, a fraction of which were in the process of migration to the center of the adrenal gland, but this was not seen in adult AMC cells. The current results raise the possibility that the mechanism for cell-to-cell communication changes in a developmental manner in rat AMC cells.

Inflammatory bowel disease is triggered by abnormalities in epithelial barrier function and immunological responses, although its pathogenesis is poorly understood. The dextran sodium sulphate (DSS)-induced colitis model has been used to examine inflammation in the colon. Damage to mucosa primality occurs in the large intestine and scarcely in the small intestine. To evaluate the effect on the ileum, we histologically analyzed the inflammatory and recovery phases in DSS model mice, and 40 kDa FITC-dextran was used to investigate barrier function. In the inflammatory phase, histological damage was insignificant. However, expanded crypts, hypertrophic goblet and Paneth cells, increased mucus production and secretion were observed. The cellular morphology was restored to that of the control in the recovery phase. According to hybridization and lectin histochemistry, the expression of intestinal stem cell markers, secretory cell differentiation factors, and glycosylation of secretory granules in Paneth cells differed in the DSS model. DSS-treatment did not influence the barrier function in the ileum, and FITC-dextran did not diffuse the paracellular pathway into the mucosa. However, cells incorporating FITC appeared even under normal conditions. The number of FITC-positive Paneth cells was lower in the DSS group than the control group. Our results showed morphological and functional alterations in ileal epithelial cells, especially secretory cells, in the DSS colitis model.