Histology and histopathology最新文献

Introduction: Colorectal cancer is the third most prevalent malignancy and the second leading cause of cancer mortality worldwide. Neoadjuvant concurrent chemoradiotherapy (CCRT) improves survival and increases curative surgery rates in rectal cancer. C20orf56, a long non-coding RNA (lncRNA), plays diverse roles in cancer, but its association with neoadjuvant CCRT response and prognosis in rectal cancer remains unexplored.

Materials and methods: Tumor samples from 343 rectal cancer patients who received neoadjuvant CCRT followed by surgery were analyzed for C20orf56 expression via in situ hybridization. Associations between C20orf56 expression and clinicopathological parameters were evaluated with the χ² test. Survival outcomes were assessed using the Kaplan-Meier method and compared by log-rank tests, while multivariate analysis was conducted using a Cox proportional hazards model. Additionally, an independent cohort of responders and non-responders (n=8 per group) was used to validate C20orf56 transcript levels by real-time RT-PCR.

Results: A transcriptomic analysis (GSE35452) identified C20orf56 as differentially expressed between responders and non-responders. Decreased expression of C20orf56 showed significant correlations with less advanced post-treatment tumor invasiveness, negative post-treatment nodal metastasis, absence of vascular invasion and perineural invasion, and improved response to neoadjuvant CCRT (all p≤0.024). Diminished expression of C20orf56 was associated not only with favorable disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS) (all p<0.0001) in univariate analysis but also functioned as an independent predictor signifying enhanced clinical outcomes, including DSS, LRFS, and MeFS (all p<0.001). In the real-time RT-PCR analysis, the transcriptomic levels were significantly lower in the responder group compared with the non-responder group (p=0.007).

Conclusion: C20orf56 may play a significant role in rectal cancer progression and response to neoadjuvant CCRT, serving as a novel prognostic factor.

Objectives: Endometritis, stemming from bacterial infection, manifests as persistent inflammation and may cause infertility. Penning decoction (PND) has been approved for clinical treatment of patients with endometritis. However, the mechanism by which it prevents endometritis remains unknown. This study aimed to examine the impact of PND on lipopolysaccharide (LPS)-induced endometritis and elucidate the underlying mechanisms involved.

Methods: Firstly, ultra-performance liquid chromatography‒quadrupole‒time‒of‒flight mass spectrometry (UPLC‒Q‒TOF‒MS) analysis, in which both positive and negative ion modes were used to identify the chemical compounds in PND, was performed. The antipyroptotic effects of PND were validated in LPS-induced endometritis mice. Additionally, mouse endometrial epithelial cells (MEECs) were used to explore the molecular mechanism of PND in serum in vitro.

Results: A total of 145 chemical compounds, including flavones, saponins, polysaccharides, alkaloids, and glycosides, were identified in positive and negative ion modes. The results showed that LPS could induce pyroptosis in endometritis in vivo and in vitro. Treatment with PND or serum containing PND could significantly ameliorate LPS-induced pyroptosis by inhibiting the activation of the TLR4/NF-κB/NLRP3 signaling pathway.

Conclusion: Our results demonstrated that PND may improve LPS-induced endometritis by inhibiting the TLR4/NF-κB/NLRP3 pathway, which provides a potentially effective drug for the clinical treatment of endometritis.

Heparan sulfate (HS), a linear sulfated polysaccharide attached to proteoglycans, modulates the availability and activity of growth factors and cytokines to regulate cell signaling, adhesion, and migration. Exostosin-1 (EXT1), a key glycosyltransferase for HS chain elongation, is increasingly implicated in cancer development and progression. Although originally identified as a tumor suppressor in hereditary multiple exostoses, EXT1 exhibits a complex, context-dependent role in cancer. The effects of EXT1 in cancer differ by cell and tumor type, exerting both tumor-suppressing and tumor-promoting effects. Notably, EXT1 also alters the tumor microenvironment via its expression in stromal fibroblasts and endothelial cells, further influencing tumor behavior. This review discusses the functions of HS and EXT1, emphasizing the roles of EXT1 in cancer and its microenvironment. A deeper understanding of these mechanisms may offer novel therapies targeting the HS biosynthetic pathway.

Background: Angiogenesis is a physiological process of diabetic wound healing. Although calycosin has been reported to exert protective effects on diabetic nephropathy, its role and mechanisms in diabetic wound healing remain unclear. This study investigates the effects of calycosin on wound healing and angiogenesis, and the role of the Nrf2/HO-1 pathway in mitigating oxidative stress in diabetic rats.

Methods: In vivo, type 2 diabetes (T2DM) in Sprague-Dawley (SD) rats was induced by a high-fat diet for six weeks combined with a single intraperitoneal injection of 45 mg/kg streptozotocin (STZ). The anesthetized diabetic rats underwent a full skin excision on the back and were then treated with calycosin for two weeks to evaluate the protective effect of calycosin on oxidative stress associated with the Nrf2/HO-1 pathway in diabetic wound rats. In vitro, damage to Human Umbilical Vein Vascular Endothelial Cells (HUVECs) was induced by high glucose, and then treated with calycosin or combined with Nrf2 agonist to evaluate whether calycosin affects cell activity and inhibits oxidative damage via the Nrf2/HO-1 pathway.

Results: Our results indicate that calycosin promotes angiogenesis by activating the Nrf2/HO-1 signaling pathway and upregulating downstream antioxidant genes, thereby accelerating wound healing. In vitro studies have also shown that Nrf2/HO-1 signaling activation can enhance the promoting effect of calycosin on cell activity and the inhibitory effect on oxidative stress in HUVECs induced by high glucose.

Conclusion: Our results show that calycosin can accelerate wound healing by promoting angiogenesis and inhibiting oxidative stress mediated by the Nrf2/HO-1 pathway, which provides a theoretical basis for the treatment of refractory diabetic wounds.

Objective: This study evaluated the histological impact of long-term caloric restriction (CR) on liver and kidney aging, assessing fibrosis, metabolic overload, and senescence-associated readouts.

Methods: Eight-week-old male C57BL/6 mice were assigned to a standard diet (SD) or 50% CR and sacrificed at 12 or 16 months. A two-month-old group served as control (n=5/group). Liver and kidney tissues were processed for Hematoxylin and Eosin (H&E), Periodic Acid-Schiff (PAS), and Masson's Trichrome staining. Immunohistochemistry (IHC) assessed SIRT1, p16^INK4a, and acetylated p53 (Lys382) in both organs, and β-galactosidase immunoreactivity (IHC-DAB) in liver. Sections underwent morphometric quantification and statistical analysis.

Results: Aged SD mice exhibited liver injury, increased PAS positivity, and collagen deposition, whereas CR attenuated these changes. The SD 16M group displayed the highest PAS positivity, while CR limited glycogen accumulation and preserved lobular architecture. In the kidney, SD animals developed tubular degeneration and architectural disruption; CR preserved renal structure and reduced tubular damage. CR was associated with higher SIRT1 immunoreactivity and lower acetylated p53, consistent with preserved SIRT1-linked deacetylation status. p16-positive cells increased with age under SD and were reduced by CR, though not fully normalized at 16 months. β-galactosidase immunoreactivity was evident in aged SD hepatocytes but minimal in CR groups.

Conclusion: Long-term CR preserves hepatic and renal histoarchitecture during aging by limiting metabolic overload, fibrotic remodeling, and senescence, accompanied by a sustained SIRT1/acetyl-p53 profile consistent with reduced p53 activation.

Programmed death-ligand 1 (PD-L1) plays a central role in immune regulation in esophageal squamous cell carcinoma (ESCC) and has been widely used as a biomarker for immune checkpoint inhibitor therapy. However, the biological and clinical significance of PD-L1 expression remains controversial, partly due to its marked spatial heterogeneity and dynamic regulation within the tumor immune microenvironment (TIME). In particular, conventional assessment methods do not sufficiently distinguish between PD-L1 expression in tumor cells and that in the surrounding stromal compartment. Accumulating evidence indicates that tumoral and stromal PD-L1 expression reflect distinct biological processes and may have contrasting prognostic and therapeutic implications. Tumoral PD-L1 expression often represents adaptive immune resistance induced by cytotoxic T-cell-derived cytokines and may serve as a surrogate marker of an immune-active tumor. In contrast, stromal PD-L1 expression integrates signals from immune cells, cancer-associated fibroblasts, and other non-neoplastic components, frequently reflecting an immune-enriched microenvironment associated with restrained tumor progression and sustained chemotherapy efficacy. Recent advances in digital pathology and artificial intelligence-assisted image analysis have enabled quantitative, compartment-specific evaluation of PD-L1 expression across whole-slide images, providing new insights into its spatial distribution and clinical relevance. These approaches facilitate refined interpretation beyond binary scoring systems such as the combined positive score or tumor proportion score. In this review, we summarize current knowledge on the regulation and pathological assessment of PD-L1 in ESCC, with particular emphasis on its compartment-specific roles in tumor cells and the stroma. By integrating biological mechanisms, methodological advances, and clinical implications, we propose a conceptual framework for spatially resolved PD-L1 evaluation that may improve prognostic stratification and support more personalized treatment strategies in ESCC.

Peptidoglycan recognition proteins (PGRPs) constitute an evolutionarily conserved family of pattern recognition molecules that detect bacterial peptidoglycan. While their antimicrobial functions have been well characterized in peripheral immunity, recent discoveries have unveiled critical roles for PGRPs in central nervous system inflammation and behavior. Among the four mammalian PGRP family members, PGLYRP1 exhibits unique expression in brain microglia and demonstrates potent pro-inflammatory properties in neurological contexts. Recently, PGLYRP1 has been shown to function as a key amplifier of neuroinflammation through a novel TREM1-Syk-Erk1/2-Stat3 signaling axis, establishing a positive feedback loop with TNF-α that perpetuates microglial activation. This review synthesizes current understanding of PGRP biology in the nervous system, with particular emphasis on molecular mechanisms of PGLYRP1, cellular sources, and behavioral consequences. We examine the structural basis of peptidoglycan recognition, cell-type-specific expression patterns, signaling pathways, and integration with other innate immune systems. Furthermore, we explore emerging connections between gut microbiome-derived peptidoglycan, blood-brain barrier penetration, and neuropsychiatric disorders. Critical knowledge gaps remain regarding physiological versus pathological roles of PGLYRP1, therapeutic targeting strategies, and translational potential. Understanding PGLYRP1-mediated neuroinflammation provides novel mechanistic insights into microbiome-brain communication and offers promising therapeutic avenues for neuroinflammatory and neurodegenerative diseases.

The presence of perineural invasion (PNI), typically defined as direct contact between cancer cells and nerves, is a well-established adverse prognostic factor following definitive treatment when identified on prostate needle core biopsy. In contrast, there are mixed data regarding the clinical significance of PNI detected in radical prostatectomy specimens. Beyond the mere presence of PNI in prostate cancer specimens, several studies have suggested that quantification of the number of PNI foci may provide additional prognostic information. Nonetheless, it remains controversial whether the patterns of PNI contribute meaningfully to the risk stratification of prostate cancer. Notably, the definition of PNI appears to remain inconsistent among pathologists, ranging from broad interpretations of focal tumor involvement in or around a nerve to strict criteria requiring complete circumferential nerve encirclement. This narrative review summarizes and discusses available data supporting or refuting the clinical impact of PNI patterns, including size, degree, or other morphologic features, in men with prostate cancer. Current evidence indicates that, at least on prostate biopsy, PNI patterns generally lack independent clinical utility, while significant data exist to support the prognostic relevance of PNI patterns in radical prostatectomy specimens (and several other types of solid tumors). Until further studies providing more solid evidence are available, it may be prudent for pathologists to document and consider any patterns as PNI, especially in prostate biopsy specimens.

Inverted urothelial papilloma (IUP) is a rare benign tumor of the urinary tract, most commonly arising in the bladder and characterized by an endophytic growth pattern. IUP primarily affects middle-aged and older men and typically presents with painless hematuria. IUP was first described in 1927 and recognized as an independent entity by the World Health Organization in 1973. It can be difficult to distinguish from urothelial carcinoma (UC), which can result in misdiagnosis and overtreatment. Genetic analyses have confirmed the benign nature of IUP. Activating mutations in RAS family genes (HRAS, KRAS, NRAS) are frequent in IUP, whereas mutations typical of UC, such as FGFR3, TP53, and TERT promoter alterations, are rare. Macroscopically, lesions are generally small, solitary, and broad-based. Histologically, IUP exhibits two architectural patterns: trabecular and glandular, which both show minimal atypia and low mitotic activity. Differentiating IUP from UC with inverted growth and benign mimickers, such as florid von Brunn's nests or cystitis cystica/glandularis, is challenging, particularly when specimen size is limited. Immunohistochemistry (KRT20, TP53, and Ki-67) may support the diagnosis but does not reliably distinguish IUP from UC in difficult cases. The standard treatment is complete transurethral resection, and recurrence rates are low. The superficial urothelial cells overlying IUP may also harbor RAS mutations, challenging the long-held assumption that these cells are morphologically and genetically normal. Future studies should investigate whether similar genetic alterations in morphologically normal urothelium occur in other urothelial tumors. This could refine understanding of early tumorigenesis and guide improved detection and risk assessment.

The transcription factor Friend leukemia integration-1 (FLI-1) is implicated in various cellular functions, including the regulation of cardiovascular function. This study aimed to elucidate the role and molecular mechanisms of FLI-1 in myocardial hypertrophy. We conducted FLI-1 overexpression interventions in ISO-induced H9C2 cells and mouse models of myocardial hypertrophy, subsequently assessing their effects on Klotho expression, cardiomyocyte hypertrophy, apoptosis, and IGF-1R/GNAI1PLCG1 signaling pathway activity. Our results demonstrated that ISO induction led to a time-dependent decrease in FLI-1 expression in H9C2 cells. Furthermore, FLI-1 overexpression enhanced Klotho expression in ISO-induced H9C2 cells and significantly inhibited ISO-induced cardiomyocyte hypertrophy and apoptosis. Furthermore, the overexpression of FLI-1 was found to attenuate the activity of the insulin-like growth factor type 1 receptor (IGF-1R)/GNAI1/PLCG1 signaling pathway in ISO-induced H9C2 cells. Notably, the silencing of Klotho negated the protective effects conferred by FLI-1 overexpression on cardiomyocyte hypertrophy and apoptosis, as well as its inhibitory impact on the IGF-1R/GNAI1/PLCG1 signaling pathway. In a murine model of myocardial hypertrophy, FLI-1 overexpression similarly exhibited a protective effect by mitigating myocardial hypertrophy and damage. These findings suggest that FLI-1 exerts a protective role in cardiac hypertrophy and apoptosis, potentially through the modulation of the Klotho and IGF-1R/GNAI1/PLCG1 pathways.