Histology and histopathology Vol.35, nº6 (2020)
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- PublicationOpen AccessOverexpression of EIF5A2 is associated with poor survival and aggressive tumor biology in gallbladder cancer(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Zheng, Xin; Gao, Lei; Wang, Bo-tao; Shen, Ping; Yuan, Xiang-fei; Zhang, Lan-Qiu; Yang, Lei; Zhang, Da-Peng; Zhang, Qi; Wang, Xi-MoGallbladder cancer (GBC) is a malignant tumor of the biliary tract. The main problem affecting the treatment of gallbladder cancer is late diagnosis and poor prognosis. EIF5A2 is one of two isoforms of the EIF5A family and is reported to be a new oncogenic protein in many human cancers. In this study, our results showed for the first time that EIF5A2 was overexpressed in GBC samples compared with non-tumor tissue. Overexpression of EIF5A2 was associated with lymph node metastasis, tumor differentiation, UICC (Union for International Cancer Control) staging, histological type, metastasis, and tumor size. Overexpression of EIF5A2 in gallbladder carcinoma tissues is also associated with poor prognosis in patients. The interference of EIF5A2 significantly inhibited the proliferation, cell cycle, migration and colony formation of GBC-SD cells in vitro. Our results suggest that EIF5A2 is a target oncogene and may be an important prognostic biomarker in the pathogenesis of gallbladder cancer.
- PublicationOpen AccessBovine oviduct epithelial cells suppress the phagocytic activity of neutrophils towards sperm but not for bacteria in vitro: Immunofluorescence and electron microscopic observations(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Marey, Mohamed Ali; Matsukawa, Haruhisa; Sasaki, Motoki; Ezz, Mohamed Aboul; Yousef, Mohamed Samy; Takahashi, Ken-ichi; Miyamoto, AkioPreviously, we reported that polymorpho- nuclear neutrophils (PMNs) are constantly existent in the bovine oviduct fluid during the pre-ovulatory stage under physiological conditions. Moreover, incubation of PMNs with bovine oviduct epithelial cells-conditioned medium (BOEC-CM) resulted in suppression of their phagocytic activity for sperm. During pathophysiological conditions, cows may be inseminated by infected semen which exposes oviductal PMNs to allogenic sperm simultaneously with pathogens. This study aimed to visually investigate the role of oviduct epithelium in regulating the phagocytic behavior of PMNs toward sperm as a physiological stimulus, with Escherichia coli (E. coli) as a pathological stimulus. In our experiment, PMNs were incubated for 2 h in BOEC-CM. Phagocytosis was then assayed by co-incubation of these PMNs either with sperm, E. coli, or latex beads. BOEC- CM significantly suppressed the direct phagocytosis of PMNs for sperm, but did not affect their phagocytic activity for E. coli or latex beads. Additionally, an investigation with scanning electron microscopy revealed that BOEC-CM suppressed the formation of DNA-based neutrophil extracellular traps (NETs) for sperm entanglement. BOEC-CM did not alter NETs formation towards E. coli. A quantification of NETs formation using an immunofluorescence microscopy showed that the areas of NETs formation for E. coli were significantly larger than those formed for sperm. Our data clearly show that the bovine oviduct, through secretions, protects sperm from phagocytosis by PMNs and eliminates bacterial dissemination through maintaining the phagocytic activity of PMNs towards bacteria
- PublicationOpen AccessAliskiren improves renal morphophysiology and inflammation in Wistar rats with 2K1C renovascular hypertension(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Pereira, Priscila G.; Rabelo, Kíssila; Silva da, Jemima F. R.; Ciambarella, Bianca T.; Argento, Juliana G.C.; Nascimento, Ana L.R.; Vieira, Aline B.; Carvalho de, Jorge J.Hypertension is characterized by persistent elevated blood pressure levels, one of the leading causes of death in the world. Renovascular hypertension represents the most common cause of secondary hypertension, and its progress is associated with overactivation of the renin angiotensin aldosterone system (RAAS), causing systemic and local changes. Aliskiren is a renin-inhibiting drug that optimizes RAAS suppression. In this sense, the objective of the present study was to analyze the morphophysiology of the left kidney in Wistar rats with renovascular hypertension after treatment with Aliskiren. Parameters such as systolic blood pressure, urinary creatinine and protein excretion, renal cortex structure and ultrastructure, fibrosis and tissue inflammation were analyzed. Our results showed that the hypertensive animals treated with Aliskiren presented a reestablishment of blood pressure, expression of renin, and renal function, as well as a remodeling of morphological alterations through the reduction of fibrosis. The treatment regulated the laminin expression and decreased pro-inflammatory cytokines, restoring the integrity of the glomerular filtration barrier. Therefore, our findings suggest that Aliskiren has a renoprotective effect acting on the improvement of the morphology, physiology and pathology of the renal cortex of animals with renovascular hypertension
- PublicationOpen AccessTriptolide inhibits tonsillar IgA production by upregulating FDC-SP in IgA nephropathy(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Li, Huining; Yang, Xinxin; Yao, Guodong; Zhang, Yanxiang; Xu, Yangyang; Cao, Yan; An, Xushu; Li, Haibo; Chen, Hui; Geng, Jingshu; Yuan, Dawei; Jin, Xiaoming; Meng, HongxueIgA nephropathy (IgAN) is primarily resulted of qualitative abnormality of IgA. The occurrence of IgAN is associated with affected tonsils which enhances the IgA production via IgA class switching and immuno-activation. Follicular dendritic cell-secreted protein (FDC-SP) was found to be a negative effect for IgA production in tonsil. The previous studies suggested that Triptolide might reduce IgA production by its immunosuppression role. Given this background, this study investigated the mechanisms underlying the role of Triptolide and FDC-SP in the generation of IgA and IgA class switching in tonsil of IgAN patients. Immunohistochemistry and reverse transcription-polymerase chain reaction revealed that the expression of FDC-SP was increased in the tonsils of IgAN patients with Triptolide treatment compared with those without treatment. Meanwhile, the expression of FDC-SP was negatively correlated with IgA inducing cytokines in the tonsils of IgAN patients treated with Triptolide, due to the significant decreased IgA-bearing cells. The expression of FDC-SP in tonsillar tissue was confirmed by double immunofluorescence. Importantly, Triptolide promoted FDC-SP secretion, and correlated negatively with decreased IgA production in isolated FDC-associated clusters, which had been isolated from patients without TW treatment previously. Our study demonstrated that Triptolide might have an impact on FDC-SP production and downregulation of IgA synthesis in the tonsils of IgAN patients, which could be a promising strategy for therapeutic intervention in IgAN patients.
- PublicationOpen AccessThe relationship between members of the canonical NF-kB pathway, tumour microenvironment and cancer specific survival in colorectal cancer patients(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Quinn, Jean A; Bennett, Lindsay; Patel, Meera; Frixou, Mikaela; Park, James H.; Roseweir, Antonia; Horgan, Paul G; McMillan, Donald C; Edwards, JoanneBackground. The aim of this study was to investigate the role of the upstream kinase TAK1 and the canonical NF-κB pathway in colorectal cancer (CRC). Immunohistochemistry was used to assess the expression of TAK1/pTAK1 and canonical NF-κB pathway members in a tissue microarray of 242 patients. The relationship between expression, the tumour microenvironment and cancer-specific survival were examined. Results. All the investigated members of the pathway were expressed in CRC tissue. In addition, cytoplasmic pTAK1 was associated with the tumour microenvironment (P=0.045) and cancer- specific survival (CSS) (P=0.032). When cytoplasmic pTAK1 was stratified by BRAF status, cytoplasmic pTAK1 expression association with CSS was strengthened (P=0.014). Cytoplasmic IKKβ was significantly associated with the inflammatory cell infiltrate (P=0.015) as graded by Klintrup Makinen grade, systemic inflammation as assessed by neutrophil- lymphocyte ratio (P=0.03) and CSS (P=0.046). On multivariate analysis cytoplasmic IKKβ was independently associated with CSS (HR 1.75,95%CI 1.05-2.91, P=0.033). Conclusion. Cytoplasmic pTAK1 was significantly associated with CSS and this was enhanced in patients with tumours that expressed wild type BRAF. High expression of cytoplasmic IKKβ was significantly associated with decreased CSS and with markers of the tumour microenvironment. These results support the hypothesis that NF-κB pathway members are poor prognostic markers in patients with CRC, but this requires to be validated in a large independent cohort