71 research outputs found
Empagliflozin Attenuates Non-Alcoholic Fatty Liver Disease (NAFLD) in High Fat Diet Fed ApoE (-/-) Mice by Activating Autophagy and Reducing ER Stress and Apoptosis
Aims/hypothesis: SGLT-2 inhibitors (SGLT-2i) have been studied as potential treatments against NAFLD, showing varying beneficial effects. The molecular mechanisms mediating these effects have not been fully clarified. Herein, we investigated the impact of empagliflozin on NAFLD, focusing particularly on ER stress, autophagy and apoptosis. Methods: Five-week old ApoE(-/-) mice were switched from normal to a high-fat diet (HFD). After five weeks, mice were randomly allocated into a control group (HFD + vehicle) and Empa group (HFD + empagliflozin 10 mg/kg/day) for five weeks. At the end of treatment, histomorphometric analysis was performed in liver, mRNA levels of Fasn, Screbp-1, Scd-1, Ppar-γ, Pck-1, Mcp-1, Tnf-α, Il-6, F4/80, Atf4, Elf2α, Chop, Grp78, Grp94, Χbp1, Ire1α, Atf6, mTor, Lc3b, Beclin-1, P62, Bcl-2 and Bax were measured by qRT-PCR, and protein levels of p-EIF2α, EIF2a, CHOP, LC3II, P62, BECLIN-1 and cleaved CASPASE-8 were assessed by immunoblotting. Results: Empagliflozin-treated mice exhibited reduced fasting glucose, total cholesterol and triglyceride serum levels, as well as decreased NAFLD activity score, decreased expression of lipogenic enzymes (Fasn, Screbp-1c and Pck-1) and inflammatory molecules (Mcp-1 and F4/80), compared to the Control group. Empagliflozin significantly decreased the expression of ER stress molecules Grp78, Ire1α, Xbp1, Elf2α, Atf4, Atf6, Chop, P62(Sqstm1) and Grp94; whilst activating autophagy via increased AMPK phosphorylation, decreased mTOR and increased LC3B expression. Finally, empagliflozin increased the Bcl2/Bax ratio and inhibited CASPASE-8 cleavage, reducing liver cell apoptosis. Immunoblotting analysis confirmed the qPCR results. Conclusion: These novel findings indicate that empagliflozin treatment for five weeks attenuates NAFLD progression in ApoE(-/-) mice by promoting autophagy, reducing ER stress and inhibiting hepatic apoptosis
Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry
Different attitudes of elderly female patients aged between 77-95 years with early breast cancer concerning surgical intervention vs primary endocrine therapy
External septal reconstruction with the use of polydioxanone foil: our experience
We present our experience and results after using polydioxanone (PDS) foil in septal reconstruction. In a period of 2 years, 12 patients who were admitted in our department with severe septal deviation and breathing problems underwent septoplasty under general anaesthesia. The nasal septum was approached via an external approach. In all patients, after resecting and exposing the septum, the removable piece after being divided into straight pieces, was sutured onto an appropriate sized PDS foil and reimplanted together between the mucoperichondrium flaps. Sutures were placed to fixate the "new septum" to the nasal dorsum and to the anterior nasal spine. The immediate postoperative course was unremarkable and in a follow-up appointment 6 months and 1 year postoperatively, one complication occurred, with septum subluxation noted in one patient. Use of PDS foil in septal reconstruction is an important surgical option for the correction of the markedly deviated nasal septum. Fixation of the straightened and replanted septum at the nasal dorsal septum border with the upper lateral cartilages and at the nasal spine is essentia
Commentary: Hernia, Mesh, and Topical Antibiotics, Especially Gentamycin: Seeking the Evidence for the Perfect Outcome…
Thyroid hormone receptor alpha (TRa) tissue expression in ductal invasive breast cancer: A study combining quantitative immunohistochemistry with digital slide image analysis
Background: In breast cancer, hormonal receptors hold promise for
developing novel targeted therapies. The thyroid exerts its actions via
the thyroid hormone receptors alpha and beta. The clinical significance
of the expression of thyroid hormone receptors in breast cancer is
unclear.
Material and methods: We studied thyroid hormone receptor alpha (TRa)
expression in 82 samples from 41 women with ductal invasive breast
cancer and no thyroid disease. We performed quantitative
immunohistochemistry with digital image analysis and correlated TRa
expression with clinicopathological parameters.
Results: TRa was expressed in both normal breast epithelium and breast
cancer, but expression in breast cancer was significantly lower. TRa was
expressed significantly less in larger and grade III tumors. Conversely,
breast cancers with lymphovascular invasion showed increased TRa
expression compared to cancers without lymphovascular invasion. TRa
expression was not significantly different between node positive and
node-negative breast cancers, or among different hormonal profiles and
intrinsic subtypes.
Discussion: This is the first-in-human study to combine quantitative
immunohistochemistry with image analysis to study TRa expression in
women with ductal invasive breast cancer and no clinical or biochemical
evidence of thyroid dysfunction. We confirm that TRa is expressed in
both normal and malignant breast epithelium and suggest that TRa
expression is downregulated during breast carcinogenesis. Larger and
higher grade breast cancers demonstrate partial loss in TRa expression.
Alterations in TRa expression take place even in the absence of clinical
or biochemical thyroid disease. The underlying mechanism of these
findings and their potential significance in survival and relapse
mandate further research. (C) 2017 Elsevier Ltd, BASO similar to The
Association for Cancer Surgery, and the European Society of Surgical
Oncology. All rights reserved
Different attitudes of elderly female patients aged between 77–95 years with early breast cancer concerning surgical intervention vs primary endocrine therapy
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