Journal of Molecular Histology最新文献

The study examined the features of the spatial organization and qualitative composition of the collagen matrix in prostate cancer (PCa) and the relationship of these parameters with the clinicopathological characteristics of the disease. Morphometric, histochemical (Masson’s trichrome staining, Picrosirius Red staining), and immunohistochemical methods were applied to analyze collagen architecture parameters in tumor tissue samples from 87 patients with stage II–IV PCa. Analysis of the quantitative parameters of the tumor collagen matrix showed that decreased collagen fiber length and width were associated with advanced tumor stages and the presence of metastases in pelvic lymph nodes and/or distant organs. An increase in collagen fiber density and alignment was observed in tumors of patients with metastases and elevated PSA levels. Qualitative assessment demonstrated that collagen fiber maturity (CMI) was lower in patients with metastases, whereas increased CMI values were associated with higher Gleason scores and grade groups. Immunohistochemical findings indicate variability in COL1A1 and COL3A1 expression within the PCa stroma; notably, COL3A1 expression was also detected in tumor cells. Elevated COL1A1 levels were recorded in PCa tissues of patients with T3-category tumors and increased PSA, whereas COL3A1 expression was primarily associated with metastatic status and higher histological grades. Correlation analysis confirmed a strong relationship between quantitative and qualitative parameters of collagen matrix architecture and the clinicopathological features of PCa. The findings suggest that the structural organization and composition of the collagen matrix play an important role in PCa progression and may serve as potential prognostic markers of disease course.

Diabetes Mellitus (DM) is a metabolic disease characterized by hyperglycemia resulting from impaired insulin secretion and resistance. Berberine (BBR) and N-acetylcysteine are anti-inflammatory and antiapoptotic compounds that have beneficial effects on diabetic complications. This study aimed to investigate the effects of BBR and NAC on the Hippocampus in an experimental diabetes model in rats. Rats were divided into 5 groups: control, diabetes (D), D + NAC, D + BBR, and D + BBR + NAC. STZ (45 mg/kg, i.p.) was administered to the other four groups except the control group. BBR and NAC (50 mg/kg/day) were given intragastrically (i.g.) to the treatment groups for 28 days. Decreased cell body size, pyknotic cells and necrotic neurons were observed in the D group. However, these pathological changes were largely improved in the D + BBR, D + NAC, and D + BBR + NAC. Stereologically, there was no significant difference between the groups in terms of hippocampus volume. The number of pyramidal neurons in CA1 was significantly decreased in the D group. But the number of CA1 pyramidal neurons was higher in both the alone and combined BBR and NAC treatment groups than in the D group. Expressions of Caspase-3, TNF-α, and IL-1β increased in the D group, while expressions of Bcl-2 and SYP decreased. But, BBR and NAC treatments decreased Caspase-3, TNF-α, and IL-1β expressions and increased Bcl-2 and SYP expressions. These results revealed that BBR and NAC can have an antidiabetic effect against the neuronal damage caused by diabetes in the hippocampus CA1 region, suppressing inflammation and apoptosis and preventing the decrease in the number of pyramidal neurons. Also, they reveal that they may modulate synaptic plasticity by increasing synaptophysin expression.

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Many investigations have indicated the significance of microRNAs (miRNAs) as potential biomarkers for early obesity in children. MiR-874-3p was revealed to be downregulated in overweight/obese children. However, the specific function and mechanism of miR-874-3p in the progression of childhood obesity remain unclear. Human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were stimulated with tumor necrosis factor α (TNF-α) to establish an in vitro cell model. CCK-8 assay and ELISA were used to assess cell viability and proinflammatory cytokine secretion, respectively. RT-qPCR was used for miR-874-3p expression analysis. Western blotting was utilized to evaluate protein levels of miR-874-3p downstream targets and nuclear factor kappa B (NF-κB) signaling-related markers. Luciferase reporter assay was conducted to verify the binding relation between miR-874-3p and nucleolin (NCL). MiR-874-3p overexpression attenuated TNF-α-induced inhibition of cell viability and promotion of proinflammatory cytokine production. Mechanistically, NCL served as a target of miR-874-3p, and overexpressing miR-874-3p inactivated NCL-mediated NF-κB signaling. Moreover, NCL upregulation reversed miR-874-3p overexpression-mediated effects on the viability and proinflammatory cytokines in SGBS adipocytes. MiR-874-3p alleviates TNF-α-induced inflammatory response in SGBS adipocytes by downregulating NCL and inactivating NF-κB signaling.

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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