Journal of Molecular Histology最新文献

Colorectal cancer (CRC) remains a major global health burden, with rising incidence and mortality, particularly in developing countries. The tumor microenvironment (TME) plays a critical role in CRC progression by facilitating angiogenesis, immune evasion, and metastasis through complex intercellular communication. Among the key mediators of this communication are exosomes—nano-sized extracellular vesicles—that transport a variety of bioactive molecules, including competing endogenous RNAs (ceRNAs). These ceRNAs, such as long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and mRNAs, act as molecular sponges for microRNAs (miRNAs), thereby regulating gene expression and influencing cancer-related pathways like Wnt/β-catenin and PI3K/Akt. This review explores the emerging role of exosomal ceRNAs derived from the TME in CRC progression, emphasizing their involvement in promoting tumor cell proliferation, invasion, metastasis, and resistance to therapy. By elucidating the intricate crosstalk between exosomal ceRNAs and the TME, we highlight their potential as novel biomarkers and therapeutic targets, offering new avenues for personalized treatment strategies in colorectal malignancies. Despite growing interest in exosomes and non-coding RNAs in colorectal cancer (CRC), limited attention has been given to the specific role of exosomal ceRNAs derived from the tumor microenvironment (TME). Existing reviews have predominantly addressed broader aspects of exosomal non-coding RNAs (e.g., miRNAs, lncRNAs, and circRNAs in general CRC progression, metastasis, or as biomarkers) or focused on exosomal communication in other malignancies. However, the intricate mechanisms by which TME-derived exosomal ceRNAs establish regulatory networks to drive CRC pathology—particularly through miRNA sponging in stromal-tumor crosstalk—remain underexplored and insufficiently synthesized. This review addresses these critical gaps by uniquely emphasizing exosomal ceRNAs sourced from the TME (including CAFs, macrophages, and other stromal components), elucidating their convergent roles in orchestrating proliferation, invasion, immune evasion, and chemoresistance. By integrating recent evidence into a TME-centric framework, we provide novel insights into potential diagnostic and therapeutic applications, advancing beyond general exosomal RNA overviews toward targeted strategies for CRC.

Tamoxifen, a selective estrogen receptor modulator (SERM), regulates estrogen signaling in a tissue-dependent manner. Phytoestrogens such as red clover (Trifolium pratense) activate estrogenic pathways through receptor agonism and are increasingly studied for hormone-related conditions. This study compared the endocrine and hepatic effects of tamoxifen and red clover extract in a validated vertebrate model, the female three-spot gourami (Trichogaster trichopterus). A total of 120 adult female gourami were randomly assigned to eight groups, receiving intramuscular (IM) injections of tamoxifen (10, 50, 100 mg/kg), IM injections of red clover extract (25, 75, 150 mg/kg), vehicle, or no treatment over 18 days. Reproductive (GSI, hormone levels, ovarian histology) and hepatic (HSI, ALT/AST levels, liver histology, TEM) parameters were assessed. Tamoxifen induced dose-dependent reductions in GSI at 50 and 100 mg/kg (p = 0.004 and p < 0.001), accompanied by significant decreases in sex hormone levels and elevations in ALT and AST (p < 0.01), along with marked hepatic histopathological changes. In contrast, red clover extract significantly increased GSI at 75 and 150 mg/kg (p = 0.012 and p = 0.001) and enhanced sex hormone levels (p < 0.05) compared with controls. Histological and ultrastructural analyses confirmed arrested ovarian development and hepatic degeneration in tamoxifen-treated fish, while red clover–treated fish showed follicular maturation and preserved liver architecture. The contrasting effects of tamoxifen and red clover reflect their distinct estrogen-modulatory mechanisms. While tamoxifen showed anti-estrogenic and hepatotoxic effects, red clover promoted reproductive activity with preserved hepatic safety, supporting its potential as a safer phytoestrogenic alternative.

This study investigated the molecular and histological responses of male rat reproductive tissues to combined radiofrequency electromagnetic field (RF-EMF) and pulsed magnetic field (PMF) exposure. Sixty adult male Wistar rats were assigned to ten groups and exposed once, twice, or three times daily for 1 day, 1 week, and 1 month. Penile, testicular, prostatic, and renal tissues were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR), histopathology, and immunohistochemistry. Dual-mode electromagnetic exposure produced a marked increase in endothelial nitric oxide synthase (eNOS) mRNA expression, particularly in long-term and higher-frequency groups, whereas vascular endothelial growth factor (VEGF) levels displayed only minimal changes. Tumor necrosis factor-alpha (TNF-α) expression decreased in penile tissue following short-term exposure but showed a mild elevation in the long-term, high-frequency testicular group, indicating localized sensitivity. Histopathological examination revealed preserved tissue architecture in the penis, prostate, and kidneys, with hyperemia being the primary finding in penile sections. Caspase-3 (Cas-3) immunoreactivity remained low across all groups, demonstrating an absence of apoptotic activation. Testicular tissues maintained overall tubular integrity, although a moderate reduction in intratubular spermatozoa was noted in the one-month high-frequency group without accompanying necrosis or apoptosis. These findings indicate that RF-EMF and PMF exposure enhances endothelial activation mainly through eNOS upregulation while maintaining general tissue integrity in male reproductive organs. The mild testicular inflammatory response observed under prolonged exposure underscores the importance of dose-dependent application. Overall, the results support the biological safety and physiological relevance of dual electromagnetic stimulation under controlled experimental conditions.

Autophagy refers to the intra-cellular metabolism pathways that deliver cytoplasmic target substances to lysosomes for degradation. When cells are exposed to stress; autophagy is developed and has the ability to maintain an adaptable method to the survival of cells. The AMPK- signaling pathway was considered an essential regulator of the autophagy during energy depletion. Many studies suggest that autophagy protects the I/R-induced renal tubular cell injury via an AMPK-regulated pathway. The aim of the current work is to study the effect of metformin on autophagy process and renal alterations associated with ischemia-reperfusion injury through examining its effect on renal functions, oxidative markers and expression of ATG7 and LC3II gene in renal tissue. Sham rats (control, n = 10); the rats in the sham group were pre-treated with saline before laparotomy, Group 2 (Ischemic-reperfusion injury, I/R, n = 20); bilateral renal pedicles were clipped for 45 min, followed by perfusion for 24 h to establish I/R model, Group 3(IR + metformin 300 mg/kg, n = 20), Animals were pre-treated with the metformin (Met) at 300 mg/kg 2 doses 2 h, 12 h prior to 45 min of ischemia. The results showed that there is disturbed renal functions as evidenced by the increase in kidney function parameters. Metformin treatment had a protective effect in group that receive treatment through up-regulation of autophagy markers ATG7 and LC3II gene & improve kidney function tests, MDA and histological findings. The results suggest that metformin-induced autophagy through activating the AMPK pathway has protection impact against kidney I/R injury.

Lung cancer, being an aggressive malignancy, is a leading cause of cancer-related mortality worldwide. Urethane, a genotoxic chemical, is a highly potent carcinogen in the development of lung cancer. Understanding the molecular mechanisms related to oxidative stress and metabolic anomalies involved in lung malignancy caused by urethane is of utmost importance. Male C57BL/6 mice were used to generate a urethane-induced lung cancer model. Urethane-exposed animals demonstrated cancerous lesions, loss of normal pulmonary architecture, and condensed alveolar structure. Urethane exposure upregulated K-Ras and downregulated p53 in the induced group. The induced rats also showed a decrease in Kelch-like ECH-associated protein 1 (KEAP1), Cullin3 (CUL3) and upregulated nuclear factor erythroid 2–related factor 2 (NRF2) and Heme oxygenase-1 (HO-1). Metabolomics studies identified that urethane exposure impacted the citric acid cycle, nucleic acid biosynthesis, amino acid, and sugar and lipid metabolism. Crucial metabolites, such as homocysteine, methylmalonic acid and 5-hydroxytryptamine (5-HT) were found to be upregulated, while tricarboxylic acid (TCA) cycle and fatty acid (FA) cycle metabolites were found to be downregulated in the urethane-induced group. Moreover, a rise in homocysteine was identified in univariate, multivariate, as well as biomarker analysis. Overall, the outcomes of the present study acknowledge the implications of key signaling and metabolic pathway modulations by urethane treatment, whose dysregulation might be associated with lung carcinogenesis.