Journal of Molecular Histology最新文献

Serrated polyps, key precursors in up to 30% of colorectal cancer (CRC) cases, present substantial diagnostic challenges due to morphological similarities, especially between sessile serrated adenomas/polyps or sessile serrated lesions (SSLs) and hyperplastic polyps (HPs). Current histopathological methods often fail to reliably differentiate these lesions, with diagnostic accuracy rates as low as 70–85%. This underscores the urgent need for molecular markers to facilitate early detection and surveillance of CRC. We integrated RNA sequencing datasets (GSE76987, GSE46513, ERP109626) using meta-analysis to identify differentially expressed genes (DEGs) distinguishing SSL from HPs. Candidate genes (FOXQ1, GRIN2D, SCNN1B) were validated using quantitative real-time PCR (qPCR) on 30 SSLs, HPs, adjacent normal tissues, and 15 CRC samples. FOXQ1 and GRIN2D were significantly upregulated in SSLs and CRC samples compared to HPs and normal tissues (P < 0.0001), while SCNN1B was consistently downregulated (P = 0.0045). These gene expression patterns were consistent across both bioinformatics and wet-lab analyses. This integrative approach identified FOXQ1, GRIN2D, and SCNN1B as promising molecular biomarkers for distinguishing high-risk SSLs from HPs. These genes hold potential for enhancing diagnostic accuracy and early CRC detection. Further functional studies are warranted to explore their roles in serrated neoplasia and clinical application in CRC risk assessment.

Undescended testes is a common medical condition that is often treated late because it is generally not recognized early. In delayed cases, the testes can be damaged by higher temperatures, which may lead to infertility and cancer. Various studies have shown that stem cells can be protective in testicular damage, and regardless of their intended use, they have generally shown a favorable safety profile in preclinical studies. Based on this data, the investigation focused on adipose-derived stem cell (ADSC) treatment to evaluate its protective effects on experimental undescended testis (EUT) damage. Forty male Wistar rats (16–19 days old) were divided into two experimental durations (3 days and 7 days, n = 20 for each duration). There were four groups in each period (n = 5/group): Control, EUT, EUT + medium (M), and EUT + ADSC. In EUT groups, the right testis was surgically affixed intra-abdominally. ADSC-treated rats were administered 1 × 10⁶ ADSCs in 300 µL of medium injected into the rete testis. Histopathological assessment was conducted using hematoxylin–eosin staining and Johnsen’s grading system. We used eNOS/iNOS immunohistochemistry and the TUNEL test to check for oxidative stress and apoptosis, and VASA immunostaining to check for germ cells. The one-way ANOVA test was used for statistical analysis. A p-value of less than 0.05 was considered significant. In EUT applied testicles, edema and interstitial space between seminiferous tubules, degeneration within seminiferous tubules, vacuolization, pyknotic cells, and atrophic structures were observed. There were notable histopathologic differences observed with medium and low amounts of ADSC. NOS immunohistochemistry was utilized to assess oxidative damage, while TUNEL was employed to detect apoptotic cell death. VASA stainings utilized as markers for spermatogonial cells exhibited high positivity in early term, peaking in the control group and subsequently decreasing, particularly notable in the EUT group. ADSC therapy reduces histopathological damage, oxidative stress, and apoptosis in the EUT model, indicating its potential for future clinical application in infertility treatment.

Gestational diabetes mellitus (GDM) is a pregnancy-associated metabolic disorder characterized by insulin resistance and hyperglycemia, posing significant risks to maternal-fetal health. While placental inflammation contributes to GDM pathology, its cellular mechanisms remain incompletely understood. Leveraging public single-cell RNA sequencing (scRNA-seq) data, we constructed a cellular atlas of GDM and control placental tissues, identifying 14 transcriptionally distinct populations. Neutrophil_1 emerged as the dominant pro-inflammatory subset, exhibiting amplified interactions with macrophages and T cells that exacerbate inflammatory responses. Pseudotime trajectory analysis revealed Neutrophil_2 as a precursor state differentiating toward the Neutrophil_1 lineage through transcriptionally regulated programming. Critically, Arginine catabolism and Nicotinate/nicotinamide metabolism were found to modulate Neutrophil_1’s pro-inflammatory functions. Our findings implicate pathogenic neutrophil subsets in GDM progression and nominate arginase and NAMPT inhibition as potential therapeutic strategies for mitigating neutrophil-mediated placental inflammation.

The use of animal models plays a crucial role in advancing our understanding of human diseases, providing valuable insights into pathophysiological mechanisms and supporting the development of innovative therapeutic strategies. Among the available models, porcine models have been recognized as particularly relevant due to their anatomical, genetic, and physiological similarities to humans. Notably, this review provides the first comprehensive comparative analysis of porcine and human salivary glands, integrating anatomical, functional, and translational perspectives. Porcine salivary glands offer a promising platform for comparative studies, as they share both structural and functional characteristics with human salivary tissue. This review highlights the anatomical and functional parallels between porcine and human salivary glands, emphasizing their significance in biomedical research. In recent years, porcine models have been increasingly employed in studies investigating disease mechanisms, drug efficacy and toxicity, as well as regenerative medicine. The integration of these models into translational research is expected to facilitate the development of novel therapeutic approaches and improve clinical outcomes in human patients. Ongoing research on the application of porcine models remains essential for refining current methodologies and expanding the scope of salivary gland studies related to human health and disease.

Anal fistula (AF) is a common anorectal disease that significantly impairs patients’ quality of life. Dressings were frequently used for therapeutic wound healing. In this study, Danshen/Huanglian-loaded gelatin/Bletilla striata gum (DH-GB) dressings were prepared. The aim was to investigate its therapeutic effects and potential mechanism in AF. DH-GB, Danshen-loaded gelatin/Bletilla striata gum (D-GB), and GB dressings were prepared. AF models were constructed using wire surgery method, with dressing treatment for two weeks. Wound healing rate and blood flow were detected during this period. HE staining, MASSON staining, and immunohistochemistry for Angiopoietins-1 (Ang-1) expression were performed. In vitro, rat primary skin flbroblast cells (PRSFs) were randomized into Control, immersion solution of dressings (Danshen/Huanglian), Danshen/Huanglian + small interfering RNA-negative control (si-NC), and Danshen/Huanglian + siRNA targeting transforming growth factor-β (si-TGF-β) groups. Cell viability and cell proliferation were assessed by CCK8 and EdU assay. Additionally, both in vivo and in vitro, ELISA for VEGF levels and Western blot for TGF-β/Smad pathway-related expression were conducted. In AF rats, DH-GB treatment up-regulated wound healing rate, collagen deposition, and blood flow, increased VEGF, Ang-1, TGF-β, p-Smad2/Smad2, p-Smad3/Smad3, and p-Smad4/Smad4 expression, and improved pathological damage. Notably, DH-GB dressings exhibited enhanced efficacy in promoting wound healing compared to D-GB and GB dressings. Moreover, in rat PRSFs, Danshen/Huanglian promoted cell viability, cell proliferation, and enhanced VEGF, TGF-β, p-Smad2/Smad2, p-Smad3/Smad3, and p-Smad4/Smad4 expression, which were reversed by si-TGF-β. Our study revealed that DH-GB dressings promoted AF wound healing by stimulating angiogenesis through up-regulating TGF-β/Smad pathway, offering scientific foundation for its clinical application in AF.

Magnesium–zinc (Mg–Zn) alloys are widely investigated as potential biodegradable biomaterials, but their systemic safety and tissue-level effects remain incompletely understood. This study aimed to evaluate the biochemical and histopathological responses to intramuscular implantation of Mg–Zn alloys in rats. Thirty-two male Wistar albino rats were randomly assigned to four groups: Control, Mg, MgZn1, and MgZn3, and sacrificed at the 4th and 7th weeks. Blood samples were collected for lipid profile, liver and kidney function tests, and protein analysis. Histopathological examinations of muscle, brain, kidney, liver, and spleen tissues were performed using hematoxylin and eosin (H&E) staining. Biochemical analysis revealed no statistically significant differences among groups (p ≥ 0.05), although the MgZn3 group showed mild elevations in kidney function markers. Histological evaluation demonstrated preserved cortical and hepatic architecture, mild edema and vascular congestion in muscle tissue, focal tubulitis and interstitial lymphocyte infiltration in kidneys, and increased numbers of debris-laden macrophages in spleen sections of MgZn3 animals. No severe or life-threatening alterations were detected. In conclusion, Mg–Zn alloys exhibited favorable short-term biocompatibility with only limited systemic and histological changes, while higher zinc content (MgZn3) was associated with mild renal and splenic responses. These findings highlight the need for further long-term studies using complementary staining methods to confirm safety for biomedical applications.

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Atrazine (2-chloro-4-ethylamino-6-isopropylamino-s-triazine) is an active component of herbicides used worldwide in agriculture. Atrazine is an endocrine disruptor, capable of interfering with the delicate hormonal balance necessary for normal reproductive function. Despite numerous studies on atrazine’s impact on male reproduction, significant gaps remain, particularly concerning the male genital tract beyond the testes. Therefore, we reviewed the effects of atrazine on the entire male reproductive system to understand the complexity of its actions. Adverse effects of atrazine on the morphophysiology of male reproductive organs, including the testes, efferent ductules, epididymis, accessory glands, and external genitalia, all crucial for male fertility, have been found. Atrazine disrupts the hypothalamic-pituitary-gonadal (HPG) axis, affects key enzymes in steroidogenesis, induces oxidative stress, and consequently disrupts spermatogenesis. Moreover, intergenerational effects are evident, with in utero exposure leading to reproductive abnormalities in offspring, and transgenerational effects have also been observed. Effects on rodent prostate and male external genitalia are concerning, considering that higher incidence of prostate cancer, cryptorchidism and hypospadias, potentially related to atrazine exposure have also been described. Given that atrazine is a globally used endocrine disruptor, further studies are required to clarify its potential involvement in these developmental disorders. Future systematic studies using environmentally relevant doses of atrazine, encompassing the entire reproductive system and its control by the HPG axis, are crucial for a thorough risk assessment.

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Sevoflurane is a cornerstone of pediatric anesthesia but poses risks for neurodevelopmental toxicity. While dysregulation of iron metabolism and autophagy have been implicated, the precise molecular link, particularly the role of NCOA4-mediated ferritinophagy in driving ferroptosis, remains a critical knowledge gap. This study aimed to determine whether and how the NCOA4-ferritinophagy-GPX4 axis mediates sevoflurane-induced neuronal ferroptosis in the developing brain. The involvement of NCOA4-mediated ferritinophagy and ferroptosis in sevoflurane-induced neurotoxicity was examined using both in vitro PC12 cell models and in vivo neonatal Sprague-Dawley rat models. In vitro, PC12 cells were exposed to sevoflurane and subsequently treated with Ferrostatin-1 (Fer-1), 3-Methyladenine (3-MA), or NCOA4-targeted siRNA. Assessments included measurements of cell viability, oxidative stress markers, and the expression levels of ferroptosis-related genes and proteins. In in vivo, neonatal rats were exposed to sevoflurane, followed by evaluation of hippocampal damage and cognitive function using Western blot analysis, hematoxylin and eosin staining, immunohistochemistry, and the Morris water maze test. Exposure to sevoflurane significantly decreased cell viability and intracellular glutathione levels while increasing levels of reactive oxygen species, malondialdehyde, and ferrous iron levels in PC12 cells. Expression of NCOA4 was upregulated, whereas GPX4 and ferritin expression were downregulated. Among the treatments, Fer-1 demonstrated greater efficacy in mitigating these changes compared to 3-MA or NCOA4 silencing. In neonatal rats, sevoflurane induced hippocampal neuronal damage, elevated NCOA4 expression and LC3-II/LC3-I ratio, reduced GPX4 and ferritin levels, and impaired spatial learning and memory. Fer-1 conferred superior neuroprotective effects compared to 3-MA. Sevoflurane induces ferroptotic neuronal death in the developing brain through activation of the NCOA4-ferritinophagy-GPX4 pathway. These findings highlight the vulnerability of the developing hippocampus to disruptions in iron metabolism and ferroptosis, and underscore the potential of ferroptosis-targeted neuroprotective strategies in pediatric anesthesia.

Fungal dysbiosis can be associated with the carcinogenesis of malignant tumors, and recent studies have indicated that Aspergillus sydowii (A. sydowii) plays a role in the pathogenesis of lung adenocarcinoma (LUAD). However, current research lacks effective treatment options for LUAD infected with A. sydowii. Therefore, the aim of this study was to investigate the therapeutic effects and mechanisms of β-ionone. Lewis lung cancer (LLC) cell xenograft tumor mouse model was constructed, and A. sydowii or various concentrations of β-ionone were treated. Subsequently, tumor volume and mass were monitored. Fluorescence in situ hybridization (FISH) staining with the D223 28S rRNA probe was employed to assess the abundance of fungi within the tumors. Additionally, immunohistochemical staining, flow cytometry, and ELISA were utilized to analyze the function of myeloid-derived suppressor cells (MDSCs) within the tumor. This study revealed that compared to the control group, A. sydowii-infected mice exhibited significantly increased tumor volume and mass (P < 0.001), enhanced Ki-67 staining intensity in tumor tissues (P < 0.01), and elevated fungal abundance within the tumor microenvironment (P < 0.001). Furthermore, A. sydowii promoted the expansion and functional activation of CD11b⁺ Gr1⁺ MDSCs. In contrast, β-ionone treatment suppressed LUAD tumor growth while concurrently inhibiting MDSC functional activation. Mechanistic investigations demonstrated that β-ionone exerts its anti-tumor and anti-fungal effects by suppressing the activation of the CARD9/p38 MAPK signaling pathway. β-ionone exhibits antitumor activity in A. sydowii-induced LUAD, which supports the potential clinical application of β-ionone in lung cancer therapy.

Sulfur mustard (SM), a highly reactive alkylating agent, remains a significant threat to both military personnel and civilian populations due to its toxic effects. Although substantial research has been conducted, the precise apoptotic mechanisms triggered by SM exposure are not yet fully understood. This study aimed to assess potential differences in the apoptosis following SM-induced acute pulmonary injury via the two routes. An acute pulmonary injury model was developed using SM at an equitoxic dose (1 LD₅₀), administered via either a single intraperitoneal injection or intratracheal instillation. Protein expression levels and mRNA expressions of cysteinyl aspartate specific proteinase-2 (caspase-2), caspase-4, caspase-7, caspase-8, p53, and factor-associated suicide ligand (FasL) were evaluated using immunohistochemistry labeling and polymerase chain reaction analysis. At equitoxic doses, the intraperitoneal SM group exhibited significantly higher protein expression ratios and mRNA expression levels of caspase-2, caspase-4, caspase-7, caspase-8, p53, and FasL in the epithelial cells of the alveolar septa from the right lower lobe of the rat’s lungs than the intratracheal SM group. Both protein and mRNA expression levels increased progressively over time in both groups. The findings indicate that SM in early-phase induces apoptosis through intrinsic and extrinsic pathways as well as possible endoplasmic reticulum stress-related pathway. These insights contribute to a deeper understanding of SM toxicity and offer a basis for developing targeted therapeutic strategies to mitigate its harmful effects.

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