Histology and histopathology Vol.34,nº10 (2019)

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http://hdl.handle.net/10201/180009

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    Differential severity of LPS-induced lung injury in CD26/DPP4 positive and deficient F344 rats
    (2019) Zientara, Alicja; Stephan, Michael; von Hörsten, Stephan; Schmied, Andreas
    Background. Lipopolysaccharide (LPS) induced inflammation often leads to lung injury, in which pulmonary recruitment of neutrophils plays a pivotal role. Inflammatory processes are influenced by CD26/DPP4, highly expressed in lungs. Asthma induced CD26/DPP4 deficient (CD26/DPP4 - ) Fischer (F) 344 rats suffering from a transport block in the rER caused by a point mutation showed reduced pulmonary inflammation and reduced expression of immuno- modulating surfactant proteins (SP). The degree of LPS induced lung injury in CD26/DPP4 deficient rats has not been investigated so far. Objective. We hypothesize that LPS induced lung injury leads not only to an attenuated inflammation but also to a reduced SP expression and decreased structural damage in CD26/DPP4 - rats. Methods. Both genotypes were intratracheally instilled with 250 μl LPS or with 250 μl 0.9% NaCl. Nine hours later animals were killed and either bronchoalveolar lavage was carried out to determine inflammatory cells and surface tension or lung blocks were removed and processed for histology, immunohistochemistry, electron microscopy or qRt-PCR analyses and Western Blot analyses. Results. Signs of acute lung injury, such as structural damage of the blood gas barrier occurred only sporadically in both genotypes. LPS-induced CD26/DPP4 - rats showed decreased gene expression of SP-A and SP-D and reduced signs of lung inflammation associated with a reduced alveolar influx of macrophages and neutrophils. Conclusions. Less pulmonary inflammation combined with less structural alterations and minor expression of immunomodulating SP may be an indication of the critical role of CD26/DPP4 in regulating lung inflammation
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    Density of CD8-positive tumor-infiltrating T-lymphocytes is an independent prognostic factor in adenocarcinoma of the esophagogastric junction
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Knief, Juliana; Lazar Karsten, Pamela; Wellner, Ulrich; Humme, Richard; Thorns, Christoph
    Tumor-infiltrating lymphocytes (TILs) have commonly been associated with markedly improved prognosis in a variety of human cancers, including carcinomas of the upper and lower gastrointestinal tract. Especially the presence of T-cells (cytotoxic as well as helper cells) seems to define a subgroup of patients with prolonged overall and event-free survival. The density of TILs was assessed via immunohistochemistry for CD8 and CD103 in a population of 228 adenocarcinomas of the esophagogastric junction. Density of CD8+ Tlymphocytes was inversely correlated with depth of tumor infiltration (p=0.013) while no correlation with any of the analyzed clinicopathologic factors could be established for CD103-density. High density of CD8- positive T-cells additionally showed significantly longer overall survival (OS) with a p-value of 0.024 while density of CD103+ cells was associated with prolonged tumor free survival (p-value 0.011). Independence could be demonstrated applying Cox proportional hazard analysis (Hazard Ratio 0.742; 95%-Confidence Interval 0.579-0.951; p=0.019). High density of CD8-positive Tlymphocytes identifies a patient subgroup with significantly prolonged overall survival, is correlated with tumor stage and might open up new therapeutic possibilities via immunomodulating drugs.
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    Harmine shows therapeutic activity on nicotine-induced liver failure in mice
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2019) Salahshoor, Mohammad Reza; Gholami mahmoudian, Zahra; Roshankhah, Shiva; Farokhi, Mehdi; Jalili, Cyrus
    This experiment evaluated the effects of harmine against nicotine-induced damage to the liver of mice. Nicotine is a major toxic component of cigarette smoke and a major risk factor for functional disorders in the liver, because it induces oxidative stress. Harmine is a harmal-derived alkaloid with therapeutic and antioxidant properties. In this study, 80 male mice were randomly assigned to 10 groups: the normal control and nicotine control groups (2.5 mg/kg); the harmine groups (5, 10, 15, and 20 mg/kg), and the nicotine + harmine groups (5, 10, 15 and 20 mg/kg mg/kg). Treatments were administered intraperitoneally daily for 28 days. Nitric oxide (NO) level, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) concentrations were determined. In addition, thiobarbituric acid reactive species, antioxidant capacity, and the diameters of the hepatocytes and central hepatic vein (CHV) were investigated. Nicotine administration significantly improved liver MDA and NO levels, CHV and hepatocyte diameters, and liver enzymes, and it decreased tissue FRAP levels compared to the normal control group (p<0.05). In the harmine and harmine + nicotine groups, in all dosages, all measured factors decreased significantly, while the FRAP tissue level increased compared with the nicotine control group (p<0.05). It seems that liver injury was improved by harmine administration in mice because of nicotine.
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    Stimulation of regenerative blastema formation in lizards as a model to analyze limb regeneration in amniotes
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Alibardi, Lorenzo
    The hypothesis here presented tries to explain why organ regeneration is present in fish and amphibians (anamniotes) but is absent in reptiles, birds and mammals (amniotes). Anamniotes possess complex life cycles including larvae and metamorphosis stages, the latter representing a physiological form of organ destruction and regeneration coded in their genome that can be reactivated in adults in the form of regeneration. Part of the genome for larvae and metamorphosis phases was likely lost in amniotes with the evolution of direct development, the potentiation of the immune system and the increase in complexity of the nervous system. These events consequently determined incapability for organ regeneration in extant amniotes with the exception of the lizard tail. This likely derives from the evolution of a mechanism of immunosuppression that allows the regeneration of the tail although the complete morphogenetic plane of tail embryogenesis is lost. The lizard model of imperfect but outstanding organ regeneration indicates the possibility to improve organ regeneration also in other amniotes. In fact, the induction of a blastema in the amputated lizard limb has stimulated the formation of short limbs containing cartilaginous bones of the femur, tibia and fibula, and these experiments foster some hope for future attempts to induce limb and digit regeneration also in mammals.
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    HDAC2 inhibitor CAY10683 reduces intestinal epithelial cell apoptosis by inhibiting mitochondrial apoptosis pathway in acute liver failure
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2019) Liu, Yang; Wang, Yao; Chen, Qian; Jiao, Fangzhou; Wang, Luwen; Gong, Zuojiong
    Introduction. Histone deacetylases (HDAC) inhibitor has the effect of anti-tumor and inhibiting apoptosis, and could inhibit the release of inflammatory factors, reducing the damage to liver and enterocytes in acute liver failure (ALF). HDAC2 specific inhibitor CAY10683 was used to verify the protective effect on acute liver failure through reducing intestinal epithelial cell apoptosis by inhibiting mitochondrial apoptosis pathway. Materials and methods. Lipopolysaccharide/D- galactosamine (LPS/D-GalN) was used to induce ALF in Sprague-Dawley rats. A total of 18 healthy rats were randomly divided into three groups. Rats in ALF group and CAY10683 group were given the same amount of normal sodium or CAY10683 2 hours before ALF model protocol was conducted. NCM460 cells were given LPS/D-GalN to establish an apoptotic model. Flow cytometry analysis was used to determine the apoptosis of enterocytes, and TUNEL assay was used to observe the apoptosis of NCM460 cells. The expression of bax was observed by immunofluorescence. The expression of histone proteins, HDAC2 and molecules in the apoptotic signaling pathway were determined by Western blotting and real-time PCR. Results. CAY10683 improves histological and functional changes in ALF model. Compared with control group, LPS/D-GalN induced massive apoptosis of rat intestinal tissues and NCM460 cells (P<0.05), and the apoptosis rate was significantly reduced after CAY10683 treatment (P<0.05). The expression of bax was increased significantly in the model groups (P<0.05), and reduced with the treatment of CAY10683 (P<0.05). Compared with the model group, CAY10683 inhibits mitochondrial apoptosis in intestinal tissues and NCM460 cells (P<0.05). Conclusion. CAY10683 reduces the damage to liver and intestinal tissue, and plays an important role in inhibiting mitochondrial apoptosis in ALF rats and in NCM460 cells
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    Immunohistochemical expression and localization of MMP-9, MMP-13, E-Cadherin and Ki-67 in road pavers' skin chronically exposed to bitumen products.
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2019) Loreto, Carla; Lombardo, Claudia; Caltabiano, Rosario; Filetti, Vera; Vitale, Ermanno; Seminara, Danilo; Castorina, Sergio; Fenga, Concettina; Ledda, Caterina; Rapisarda, Venerando
    To investigate the matrix metalloproteinase (MMP)-9, (MMP)-13, E-Cadherin and Ki-67 expressions in road pavers’ skin chronically exposed to bitumen products in order to contribute to a better understanding of the earlier tissue alteration. Skin punch biopsies from 16 daily exposed workers and a control group were studied by immunohistochemistry. Morphometric and densitometric analyses were also conducted. Morphological specimen evaluation of skin of road pavers showed epidermal thinning, flattening and loss of intercellular junction with a decreased expression of E-cadherin confined to the basal skin layer, together with MMP-9 and MMP-13 overexpressions in all epidermis layers, vascular structures and adnexa. No immunohistochemical alteration was reported for Ki-67 vs normal skin. Results from this study show that overexpression of MMP-9 and MMP-13 may represent an early response of the first human barrier to exposure to bitumen products. Regulation of MMPs could be one of the strategies to prevent primary skin disease.
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    Zinc finger proteins and regulation of the hallmarks of cancer
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2019) Ye, Qin; Liu, Jiayang; Xie, Ke
    Zinc finger proteins (ZFPs) form one of the largest families of transcription factors in human genetics, via their conserved zinc finger motifs. ZFPs function in many biological processes including development, differentiation, metabolism and apoptosis. In addition, recent studies have demonstrated that ZFPs are closely associated with different stages of cancer development. One of the hallmarks of cancer is altered signal transduction cascades and an understanding of the changes in these pathways is essential for targeted cancer therapy. In this review, we discuss examples of ZFPs involved in development and progression of several types of cancer, which can provide new insights into cancer treatment
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    Modulatory effect of inulin with soya isoflavones on plasma lipid profile and liver SCD-18 index in rats with induced type-2 diabetes mellitus
    (Universidad de Murcia.Departamento de Biologia Molecular e Histiologia, 2019) Misiakiewicz Has, Kamila Daria; Maciejewska, Dominika; Kolasa Wołosiuk, Agnieszka; Pilutin, Anna; Rzeszotek, Sylwia; Wilk, Aleksandra; Szypulska Koziarska, Dagmara; Stachowska, Ewa; Łukomska, Agnieszka; Wiszniewska, Barbara
    Obesity and type-2 diabetes are often associated with nonalcoholic fatty liver disease (NAFLD). Soya isoflavones act as antidiabetic agents and protect against NAFLD. There are data suggesting that inulin may increase the plasma concentration and effect of soya isoflavones. The aim of the present study was to compare the effect of soya isoflavones, as opposed to the effect of soya isoflavones with inulin, on plasma lipid profile, liver morphology, and liver fatty acids in rats with induced type-2 diabetes mellitus. Data were collected on thirty-six male Sprague- Dawley rats divided into control and diabetic groups. Animals in the diabetic (DM) group were on a high-fat diet and were injected with low doses of streptozotocin. Animals in the control groups were fed a regular diet and were injected with a buffer. After the injections, the animals were divided into three groups of nondiabetic rats (nDM)-controls (c-nDM), rats treated with isoflavones (IS-nDM), and rats treated with isoflavones plus inulin (IS+IN-nDM)-and three parallel diabetic (DM) subgroups: controls (c-DM), rats treated with isoflavone (IS-DM), and rats treated with isoflavones plus inulin (IS+IN-DM). Hepatic steatosis and fibrosis were examined using hematoxylin-eosin staining and Mallory’s trichrome methods respectively. Liver fatty acids were extracted and analyzed by gas chromatography. A lipid blood test was performed. The study showed significant changes in liver fatty acids, liver morphology, and plasma lipid profile. The estimated SCD-18 index significantly decreased in both the control and DM groups after isoflavone supplementation. The level of liver steatosis and fibrosis also decreased after isoflavone supplementation in the DM groups. The plasma lipid profile showed increased levels of HDL-C after isoflavone supplementation in the DM groups. These results support the protective use of isoflavones in liver steatosis and as beneficial to plasma lipid profile in individuals with diabetes. A novelty of this work is its comparison of supplementation using soya isoflavones with supplementation using both soya isoflavones and inulin. Surprisingly, additional supplementation with inulin modulates the positive effect of isoflavones