Histology and histopathology Vol.38, nº4 (2023)
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- PublicationOpen AccessDownregulation of desmoglein 2 promotes EMT progression in gallbladder cancer(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, LingLing; Lv, You; Li, JinBin; Nan, YongShan; Piao, LongZhen; Liang, ZheLongObjective. To explore the correlation between the expression level of Desmoglein 2 (DSG2) and the epithelial-mesenchymal transition (EMT) progression in gallbladder cancer (GBC). Method. 106 GBC tissue specimens and corresponding clinical information were collected to make a tissue microarray. Immunohistochemical method was used to test the expression level of DSG2 in GBC tissues. DSG2 was knocked down in the GBC cell line GBC-SD to detect the change of its invasion and metastasis ability. Then RT-qPCR and Western Blot were applied on the DSG2-knocked down GBC-SD cells to detect the expression level change of genes associated with EMT. Result. The high expression rate of DSG2 was significantly correlated with the N, M and TNM staging of patients (P<0.05). Survival analysis identified that GBC patients with high DSG2 expression level had significantly better survival (P<0.05). To further investigate the potential mechanism of DSG2 on regulating GBC tumor progression, we used knockdown DSG2 on GBC-SD cell lines. The results showed that GBC-SD cell lines with DSG2 knockdown showed a promotion of cell invasion and metastatic ability. The mRNA levels of EMT-related genes E-Cadherin, Snail, Twist, ZEB1, and β-catenin, which is a key protein in the Wnt signaling pathway, were also significantly altered. Besides, protein levels of E-cadherin and Snail showed consistent results. Conclusion. The downregulation of DSG2 in gallbladder cancer is hypothesized to be associated with the invasion and metastasis progression of gallbladder cancer cells by regulating EMT-related pathways. Its expression level can be a novel biomarker for gallbladder cancer, providing new perspectives for diagnosis and treatment strategies.
- PublicationOpen AccessMaternal undernutrition model of two generations of rats: Changes in the aged retina(Universidad de Murcia. Departamento de Biología Celular e Histología, 2023) Laurinaviciute, Guoda; Simkunaite-Rizgeliene, R.; Zalgeviciene, V.; Cepuliene, R.; Jakimaviciene, E.M.; Galgauskas, S.; Petroska, D.; Besusparis, J.; Tutkuviene, J.The impact of maternal undernutrition on morphological changes of the retina was assessed in two generations of aged offspring. Wistar 18 rats (9 of each generation of 20-month-old female offspring; in total -27 eyes) were analyzed. The first generation offspring were born to mothers who: (a) were restricted to food only before pregnancy (pre-pregnancy); (b) whose food was restricted before and during pregnancy. The control group and all the offspring were fed normally. After enucleating the eyes, paraffin sections were stained with hematoxylin and eosin. The thickness of retina layers was measured. Cryosections were immunostained using glial fibrillary acidic protein, ionized calcium-binding adaptor molecule1, RNA-binding protein with multiple splicing for evaluation of macroglia, microglia and retinal ganglion cells by digital image analysis tools. Our data have shown atrophy of photoreceptor layer and degeneration of outer nuclear layer in all investigated groups, but less damage was found in the control group. Higher Müller cell activity and greater number of microglial cells was observed in the second generation offspring born from both restricted diet groups. Higher numbers of microglial and retinal ganglion cells were observed in the second generation in comparison to the first generation offspring. Malnutrition of the mother may be one of the possible causes of degeneration of the outer layers of the retina and activation of Müller cells in the second generation offspring. The effect of maternal nutritional restriction on the number of microglial and retinal ganglion cells is unclear
- PublicationOpen AccessThe clinicopathological and prognostic significances of CDC73 expression in breast cancer: A pathological and bioinformatics analysis(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) E, Ying; Xue, Hang; Zhang, Cong Yu; Zhao, Ming Zhen; Zheng, Hua-ChuanParafibromin is a protein encoded by the oncosuppressor CDC73 gene, whose mutation results in hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid carcinoma. Down-regulation of parafibromin is linked to lung, gastric, colorectal, and ovarian cancer tumorigenesis. Parafibromin expression was detected by RT-PCR, bioinformatics analysis, Western blot, and immunohistochemistry; and compared with clinicopathological characteristics of breast cancer. CDC73-related genes and pathways were analyzed using bioinformatics analysis. Parafibromin expression was increased in breast cancer compared to normal tissues at both mRNA and protein levels (p<0.05). Among triplenegative breast cancers, it was higher in basal-like 1 than basal-like 2 patients (p<0.05) and mesenchymal than immunomodulatory patients (p<0.05). CDC73 mRNA expression was positively correlated with white race, non-infiltrating immune cells, favorable luminal subtypes of PAM50, and prognosis of breast cancer patients (p<0.05). The differential genes of CDC73 were classified into enzyme inhibitors, peptidase, and keratinization by KEGG (p<0.05). Similarly, it was classified into ribosomes, TGF-β, oxidation phosphorylation, inositol phosphate metabolism, arachidonic acid metabolism, linoleic acid metabolism, ERBB, and VEGF signaling pathways by GSEA (p<0.05). The positively-correlated genes of CDC73 were involved in cell mobility, response to interferon α, nuclear pore and basket, and histone methyltransferase. The negatively-correlated genes of CDC73 were involved in the mitochondrial respiratory chain, thermogenesis, and ribosomes. Parafibromin expression was higher in invasive ductal than lobular carcinoma (p<0.05) and mucinous adenocarcinoma than others (p<0.05). Parafibromin immunoreactivity as an independent factor was positively associated with an increased overall survival rate of breast cancer patients (p<0.05). These findings suggest that up-regulation of parafibromin in breast cancer patients is closely linked to a favorable prognosis. It is involved in tumorigenesis and subsequent progression by regulating metabolism, ribosomes, and cytokines.
- PublicationOpen AccessDownregulation of miR-527 alleviates sepsisinduced acute kidney injury via targeting Beclin1(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Xu, Ke; Mo, Xiaojun; Wang, Yijun; Zeng, Zhenhua; Xu, Ziqiang; Yue, Dongyou; Li, Guicheng; Li, Tao; Liu, Junhong; Yuan, JieminBackground. Sepsis-induced acute kidney injury (AKI) is known to result from the inflammatory responses. MiRNAs participate in the development of sepsis-induced AKI. Nevertheless, the function of miR527 in sepsis-induced AKI remains unclear. Methods. Cell viability was evaluated by CCK8 assay, and TUNEL staining was applied to assess cell apoptosis. Pro-inflammatory cytokine (TNF-α, IL-6 and IL-1β) levels were evaluated by ELISA. Meanwhile, the relation among miR-527 and Beclin1 was detected by dual luciferase report assay. Western blot and RT-qPCR were used to examine the protein and mRNA levels, respectively. Furthermore, an in vivo model was constructed to assess the function of miR-527 in sepsisinduced AKI. Results. MiR-527 downregulation significantly alleviated the symptoms of sepsis-induced AKI in mice. MiR-527 level in HK-2 cells was significantly upregulated by LPS, and downregulation of miR-527 notably reversed LPS-induced inhibition of HK-2 cell viability by inhibiting apoptosis. In addition, LPS greatly increased TNF-α, IL-6 and IL-1β levels in supernatant of HK-2 cells, while miR-527 inhibitor partially restored this phenomenon. Meanwhile, Beclin1 was found to be the downstream mRNA of miR-527, and miR-527 inhibitor notably upregulated the level of LC3. MiR-527 downregulation reversed LPS-induced HK-2 cell injury through suppression of TGF-β pathway. Conclusion. Downregulation of miR-527 alleviated sepsis-induced AKI via targeting Beclin1. Thus, miR527 might act as a vital mediator in sepsis-induced AK
- PublicationOpen AccessExosomes derived from endothelial progenitor cells ameliorate glyoxylate deprivation (OGD)-induced neuronal apoptosis by delivering miR-221-3p(Universidad de Murcia. Departamento de Biología Celular e Histología, 2023) Pan, Jie; Wu, Tingting; Chen, Bo; Wu, HuadongThis study evaluated the potential of endothelial progenitor cell (EPC)-derived exosomes as a therapeutic factor for neuronal apoptosis. Mouse EPCs were cultured in vitro, and exosomes were isolated and identified using transmission electron microscopy (TEM), particle size analysis and by determining the protein expressions of exosome markers (CD9, CD63 and Alix). The apoptotic rate of OGD-treated neurons was detected by Flow cytometry assay. The mRNA and protein expression levels were detected by RT-PCR and Western blot assay, respectively. Luciferase reporter assays determined the interaction between miR-221-3p and Bcl2l11. The results showed that most exosomes are 80-120 nm in diameter. Western blot assay showed that CD9, CD63 and Alix were enriched in exosomes. EPCderived exosomes ameliorated OGD-induced neuronal apoptosis. Mechanistically, miR-221-3p from EPCderived exosomes decreased the expression of bcl2l11 in OGD-induced neuronal apoptosis. Moreover, exosomes from miR-221-3p mimics transfected EPCs reduced OGD-induced neuronal apoptosis. In conclusion, miR221-3p in EPC derived exosomes ameliorates OGDinduced neuronal apoptosis, which establish its potential as a new therapeutic method for patients with cerebrovascular diseases.