Search

The temperature resistance of glued timber, which is crucial for glued wood construction, represents a significant assessment criterion. To gain insights into this aspect, this study utilized methods such as a shear strength test in accordance with EN 302-1:2013-06 under thermal loading (from 20 °C to 200 °C), and Differential Scanning Calorimetry (DSC) to determine the glass transition temperature (Tg). An increase in thermal load resulted in a decrease in shear strength and an increase in wood breakage. A hierarchy of adhesive groups was established based on strength performance and wood failure percentage (WFP) at 200 °C. Thermoset adhesives (MF: Melamine Formaldehyde, PRF: Phenol Resorcinol Formaldehyde) led the ranking, followed by elastomer adhesives (1C-PUR: One-Component Polyurethane, EPI: Emulsion Polymer Isocyanate), with thermoplastic adhesive (PVAc: Polyvinyl Acetate) last. Thermoset adhesives further cured under heat. PUR adhesives exhibited higher strength performance at 150 °C and lower temperatures.

The mechanical properties of cured wood adhesive films were tested in a dry state by means of nanoindentation. These studies have found that the application of adhesives have an effect on the accuracy of the hardness and elastic modulus determination. The highest values of hardness among the tested adhesives at 20 °C have condensation resins: MF (0.64 GPa) and RPF (0.52 GPa). Then the decreasing EPI (0.43 GPa), PUR (0.23 GPa) and PVAc (0.14 GPa) adhesives. The values of the elastic modulus look a little bit different. The highest values among the tested adhesives at 20 °C have EPI (11.97 GPa), followed by MF (10.54 GPa), RPF (7.98 GPa), PVAc (4.71 GPa) and PUR (3.37 GPa). X-ray micro-computed tomography was used to evaluate the adhesive joint by the determination of the voids. It has been proven that this value depends on the type of adhesive, glue quantity and reactivity. The highest values of the void ratio achieve the PUR (17.26%) adhesives, then PVAc (13.97%), RRF (6.88%), MF (1.78%) and EPI (0.03%). The ratio of the gaps increases with the higher joint thickness. A too high proportion of voids may weaken the adhesive joint.

Background: Recent clinical trials on ovarian cancer with mifepristone (MF) have failed, despite in vitro findings on its strong progesterone (P4) antagonist function. Methods: Ovarian cancer human and murine cell lines, cultured high-grade human primary epithelial ovarian cancer (HG-hOEC) cells and their explants; as well as in vivo transgenic mice possessing ovarian cancer were used to assess the molecular mechanism underlying mifepristone (MF) agonistic actions in ovarian cancer progression. Findings: Herein, we show that ovarian cancer cells express traceable/no nuclear P4 receptor (PGR), but abundantly P4 receptor membrane component 1 (PGRMC1). MF significantly stimulated ovarian cancer cell migration, proliferation and growth in vivo, and the translocation of PGRMC1 into the nucleus of cancer cells; the effects inhibited by PGRMC1 inhibitor. The beneficial antitumor effect of high-doses MF could not be achieved in human cancer tissue, and the low tissue concentrations achieved with the therapeutic doses only promoted the growth of ovarian cancers. Interpretation: Our results indicate that treatment of ovarian cancer with MF and P4 may induce similar adverse agonistic effects in the absence of classical nuclear PGRs in ovarian cancer. The blockage of PGRMC1 activity may provide a novel treatment strategy for ovarian cancer. Fund: This work was supported by grants from the National Science Centre, Poland (2013/09/N/NZ5/01831 to DP-T; 2012/05/B/NZ5/01867 to MC), Academy of Finland (254366 to NAR), Moikoinen Cancer Research Foundation (to NAR) and EU PARP Cluster grant (UDA-POIG.05.01.00-005/12-00/NCREMFP to SW). Keywords: Ovarian cancer, Mifepristone, Progesterone, Nuclear progesterone receptors, Progesterone receptor membrane component 1

Abstract Background While working on CAD/CAM-customized abutments, the use of standard impression copings with a circular diameter produces inconsistency within the emergence profile. It may begin with a collapse of the supra-implant mucosa during impression taking, then lead to a computer-generated mismatch of the position and outline of the abutment shoulder, and consequently result in a compromised outcome of anticipated treatment. The aim of the study was to compare the virtual and clinical positions of the abutment shoulder in relation to the mucosal margin after the abutment delivery. Methods Conventional open-tray impression takings followed uncovering surgery. Master casts were scanned with a desktop scanner. Clinical examinations took place after abutment’s insertion and temporization (T1) and prior to cementation of the definitive crown (T2). The distances between the abutment shoulder and marginal soft tissue were measured intraorally in four aspects and juxtaposed with those on the virtual model. Results The study evaluated 257 dental implants and CAD/CAM-customized abutments. As T1 and T2 showed, there was a positive correlation between the virtually designed abutment shoulder position and matching clinical location relative to the mucosal margin. In 42.1% of cases, the distance between the mucosal margin and the abutment shoulder did not change. It increased in 36.3% of cases while a decrease occurred in 21.6% of them. Conclusions Computer-set position of the abutment shoulder in relation to the mucosal margin can be predictably implemented in clinical practice.

The following article provides the outline of the right to information on activities of the persons discharging public functions and public organs in the Republic of Poland. The article considers the structure of the right established in the Constitution of 2 April 1997 and its connection with freedom to receive and impart information.

Myxomas are the most common non-invasive but life-threatening cardiac neoplasms due to obstruction of heart chambers and risk of embolism in a manner resembling thromboembolism as well. They can occasionally disseminate via their detached fragments into the bloodstream to seed and grow as secondary still benign tumors. In this study we evaluated morphological and clinical aspects of 14 ancient, degenerated left or right-sided cardiac atrial myxomas with expression of CD9 and CD63, which are found to contribute to platelet activation, aggregation and, as a result, intratumoral thrombosis or fragmentation. The appearance of tumors varied from sessile to polypoid revealing that a higher rate of endocardial thrombosis was associated with sessile compared to polypoid myxomas and left-sided tumors compared to right-sided ones in our study. In the general aspect of ancient calcifications, amorphous calcification with intra-tumor thrombosis was noted more frequently in sessile tumors, while well-formed osseous metaplasia was usually a feature of polypoid tumors. In our material osseous metaplasia did not coexist with massive thrombosis and was found in polypoid, pedunculated myxomas. Most importantly, CD9 overexpression was recorded in every studied myxoma and CD63 gave a weak reaction in myxoma cells.

Glaucoma is a result of increased intraocular pressure leading to damage to retinal ganglion cells andoptic nerve axons. The aim of this study was to evaluate HIF-1 expression in optic nerve axons and retinalganglion cells in 42 eyes enucleated because of complete glaucoma compared to eyes removed because of injury.The immunohistochemical reaction was done and specimens were examined under a light microscope. 57% ofcases presented HIF-1 expression in the optic nerve axons, and 52.3% in the retinal ganglion cells. 20 out of 42(47.6%) cases were HIF-1 positive both in the optic nerve axons and in the retinal ganglion cells, and the stainingwas evident mostly in the nuclear and perinuclear area. Our present results indicate that HIF-1 expression inhypoxic conditions in glaucoma might be a very crucial stage in damage to retinal ganglion cells and optic nerveaxons, and might be a successful target for the implementation of neuroprotective drugs.Glaucoma is a result of increased intraocular pressure leading to damage to retinal ganglion cells andoptic nerve axons. The aim of this study was to evaluate HIF-1 expression in optic nerve axons and retinalganglion cells in 42 eyes enucleated because of complete glaucoma compared to eyes removed because of injury.The immunohistochemical reaction was done and specimens were examined under a light microscope. 57% ofcases presented HIF-1 expression in the optic nerve axons, and 52.3% in the retinal ganglion cells. 20 out of 42(47.6%) cases were HIF-1 positive both in the optic nerve axons and in the retinal ganglion cells, and the stainingwas evident mostly in the nuclear and perinuclear area. Our present results indicate that HIF-1 expression inhypoxic conditions in glaucoma might be a very crucial stage in damage to retinal ganglion cells and optic nerveaxons, and might be a successful target for the implementation of neuroprotective drugs.

Papillomas and squamous cell carcinomas are the most common conjunctival and eyelid lesions. The etiology is still unclear and recently human papillomavirus infection and p53 gene mutation have been taken into consideration. The aim of our study was the evaluation of HPV DNApresence and p53 gene mutation in 45 benign and 38 malignant squamous lesions of the conjunctiva and eyelid. For HPV detection PCR-RFLP and immunohistochemical reaction were used; for p53 gene mutation PCR-SSCP was used. Only 8.8% papillomas, 9.1% squamous cell cancers and 3.7% basal cell cancers (using PCR-RFLP method) and 26.6% papillomas, 7.4% squamous cell cancers and 9.1% basal cell cancers (using immunohisto-chemical reaction) were HPV positive. p53 gene mutation was evaluated in 24.4% papillomas, 54.5% squamous cell cancers and 22.2% basal cell cancers; most commonly in 6 and 7 exon. Human papillomavirus infection, opposite to p53 gene mutation, is not a significant etiological factor of the benign and malignant conjunctival and eyelid lesions development.

Apoptosis may occur via a death receptor-dependent or independent (mitochondrial) pathway. The mitochondrial pathway is regulated by small molecules, such as smac/Diablo, which activates caspase cascades. This study examined smac/DIABLO expression in 76 patients with endometrioid endometrial cancers. Presence of smac/DIABLO was quantified by Western blot analysis using nonfixed fresh frozen tissues. Its appearance was found in 55 (72%) of examined tumors. Smac/DIABLO expression significantly correlated with tumor grade (p

The aim of the present study was to characterize the expression pattern of tumor necrosis factor (TNF)-alpha and its receptors (TNF-Rs) in the epithelial ovarian cancer (EOC) and compare these results with the outcome of 126 patients. Presence of TNF-alpha, TNFR-1 and TNFR-2 were studied by Western blotting and immunohistochemistry. The proportion of samples positive for TNF-alpha and TNF-R2 was higher in epithelial ovarian cancer patients than in benign ovarian diseases (p

Apoptosis may occur via a death receptor-dependent or independent (mitochondrial) pathway. The mitochondrialpathway is regulated by small molecules, such as smac/Diablo, which activates caspase cascades. This study examinedsmac/DIABLO expression in 76 patients with endometrioid endometrial cancers. Presence of smac/DIABLO was quantifiedby Western blot analysis using nonfixed fresh frozen tissues. Its appearance was found in 55 (72%) of examined tumors.Smac/DIABLO expression significantly correlated with tumor grade (p

Papillomas and squamous cell carcinomas are the most common conjunctival and eyelid lesions. The etiology isstill unclear and recently human papillomavirus infection and p53 gene mutation have been taken into consideration. Theaim of our study was the evaluation of HPV DNApresence and p53 gene mutation in 45 benign and 38 malignant squamouslesions of the conjunctiva and eyelid. For HPV detection PCR-RFLP and immunohistochemical reaction were used; for p53gene mutation PCR-SSCP was used. Only 8.8% papillomas, 9.1% squamous cell cancers and 3.7% basal cell cancers (usingPCR-RFLP method) and 26.6% papillomas, 7.4% squamous cell cancers and 9.1% basal cell cancers (using immunohistochemicalreaction) were HPV positive. p53 gene mutation was evaluated in 24.4% papillomas, 54.5% squamous cell cancersand 22.2% basal cell cancers; most commonly in 6 and 7 exon. Human papillomavirus infection, opposite to p53 genemutation, is not a significant etiological factor of the benign and malignant conjunctival and eyelid lesions development.

Abstract Central nervous system hemangioblastomas (cHAB) are rare tumours which most commonly arise in the cerebellum. Most tumours are sporadic, but as many as one third of cHABs occur in the course of the hereditary disorder - von Hippel-Lindau disease (VHL). In order to diagnose new VHL families in Poland we performed sequencing of the entire VHL gene in archival material (paraffin embedded hemangioblastoma tissues) in a large series of 203 unselected patients with cHAB. VHL gene mutations were detected in 70 (41%) of 171 tumour samples from which DNA of relatively good quality was isolated. We were able to obtain blood samples from 19 of mutation positive cases. Eight (42%) of these harboured germline mutations in persons from distinct undiagnosed VHL families.

Résumé Nous rapportons l’observation d’un garçon de sept mois qui a présenté un syndrome d’entérocolite induite par les protéines lors de la première consommation de poulet. Sa mère avait elle-même un antécédent de syndrome d’entérocolite induite par les protéines pour l’œuf de poule et le poulet dans l’enfance. Notre observation illustre les difficultés diagnostiques lors du premier épisode en raison des signes cliniques et biologiques. En outre, nous attirons l’attention sur les désordres métaboliques identifiés en phase aiguë, notamment l’hyperglycémie et l’hyperlactatémie, témoins de souffrance tissulaire. Summary We report the case of a seven-month-old infant with a food protein-induced enterocolitis syndrome due to eating chicken. Surprisingly, the symptoms occurred after his first ingestion of chicken. Of interest, his mother also had also a history of a food protein-induced enterocolitis syndrome due to chicken and chicken eggs which began before the age of five years. Our case illustrates how difficult this diagnosis can be in the initial acute phase due to its various clinical signs and laboratory findings. In addition, attention should be paid to the metabolic disorders, including hyperglycemia and hyperlactatemia, which can be identified in the acute phase of enterocolitis; they may be the result of tissue damage. [ABSTRACT FROM AUTHOR]

Summary: Background: The aim of the study was clinical evaluation of photodynamic therapy efficacy in the treatment of oral leukoplakia lesions. Methods: Twenty-three consecutive patients aged 21–79 were included to the study. In all patients 44 homogeneous, flat leukoplakia lesions were clinically diagnosed and confirmed histopathologically. Photodynamic therapy was performed with the use of Photolon® photosensitizer, containing 20% Chlorine-e6 and 10% dimethyl sulfoxide and a semiconductor laser, with power up to 300mW and a wavelength of 660nm. Ten illumination sessions were conducted with the use of superficial light energy density of 90J/cm2. Results: At baseline the mean size of leukoplakia lesion was 6.5±5.10cm2 while after photodynamic therapy 3±2.99cm2. Significant reduction (on average by 53.8%) of leukoplakia lesions sizes was observed after therapy. Twelve (27.27%) lesions had been completely cured, 22 (50%) partially cured, although 10 (22.73%) lasted unchanged. The efficacy of PTD was comparable in women and men irrespective of age. There have been no adverse site effects during therapy noted. Conclusions: Within the limits of the study it can be concluded that photodynamic therapy with the use of Chlorine-e6 can lead to considerable reduction of oral leukoplakia lesions size thus may be useful in clinical practice. However there is a need of further studies on larger number of cases and longer follow-up time. [Copyright &y& Elsevier]

Objective: To study the specific mechanisms through which progesterone and selective progesterone receptor modulators impact the growth, synthesis, and accumulation of the extracellular matrix in uterine leiomyomas., Design: Laboratory study., Setting: Academic Research Institutions., Patients (s): This study involved reproductive-age women diagnosed with infertility associated uterine leiomyomas who underwent myomectomy either after selective progesterone receptor modulator ulipristal acetate (UA) treatment or without any pharmacological pretreatment. Control samples included healthy myometrium tissue (n = 100). Specimens were obtained from the Department of Reproduction and Gynecological Endocrinology and Biobank, Medical University of Bialystok, Poland., Interventions: Daily (5 mg/d) UA treated for 2 months (n = 100) and untreated (n = 150) patients with uterine leiomyomas or normal healthy myometrium (n = 100) tissue samples immediately after surgery were collected for transcriptional analysis and assessments., Main Outcome Measures: Progesterone-induced activation of the signaling pathways related to uterine leiomyomas extracellular matrix synthesis, deposition, and growth, as well as the expression profile of progesterone receptors in uterine leiomyomas, were assessed., Results: The results indicated that progesterone activated the transforming growth factor-β and SMAD3 signaling pathways and promoted proliferation, growth, and extracellular matrix remodeling in uterine leiomyomas by up-regulating SMAD3, transforming growth factor-β (TGF-β) receptor type 1 and II, Ras homolog A, vascular endothelial growth factor, or increasing the fibrosis-related gene collagen, type I, ɑ-1, and procollagen, type I, ɑ-1 production. In contrast, UA had inhibitory effects on these processes. The study also showed that both nuclear and membrane progesterone receptors play distinct roles in uterine leiomyoma pathobiology., Conclusions: We showed that both nuclear and membrane progesterone receptors were relevant in the treatment of uterine leiomyomas, especially when combined with selective progesterone receptor modulators. Novel therapeutic approaches combining selective progesterone receptor modulators with or without direct and indirect extracellular matrix targeting through selected specifically TGF-β and SMAD3 (SMAD3, TGF-β receptor types 1 and II, Ras homolog A, vascular endothelial growth factor, collagen, type I, ɑ-1) signaling pathways could therefore be a treatment option for uterine leiomyomas., Competing Interests: Declaration of Interests G.M. has nothing to disclose. D.P.T. has nothing to disclose. P.B. has nothing to disclose. O.L. has nothing to disclose. M.Sz. has nothing to disclose. M.S. has nothing to disclose. A.P.P. has nothing to disclose. M.K. has nothing to disclose. T.B. has nothing to disclose. M.Z.K. has nothing to disclose. A.P. has nothing to disclose. J.T. has nothing to disclose. X.L. has nothing to disclose. I.H. has nothing to disclose. S.W. has nothing to disclose. N.A.R. has nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Zona pellucida 3 (ZP3) expression is classically found in the ZP-layer of the oocytes, lately shown in ovarian and prostate cancer. A successful ZP3 ovarian cancer immunotherapy in transgenic mice suggested its use as an attractive therapeutic target. The biological role of ZP3 in cancer growth and progression is still unknown. We found that ~88% of the analyzed adenocarcinoma, squamous and small cell lung carcinomas to express ZP3. Knockout of ZP3 in a ZP3-expressing lung adenocarcinoma cell line, significantly decreased cell viability, proliferation, and migration rates in vitro. Zona pellucida 3 knock out (ZP3-KO) cell tumors inoculated in vivo in immunodeficient non-obese diabetic, severe combined immunodeficient mice showed significant inhibition of tumor growth and mitigation of the malignant phenotype. RNA sequencing revealed the deregulation of cell migration/adhesion signaling pathways in ZP3-KO cells. This novel functional relevance of ZP3 in lung cancer emphasized the suitability of ZP3 as a target in cancer immunotherapy and as a potential cancer biomarker., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Uterine leiomyomas (ULs) are the most common benign smooth muscle cell steroid-dependent tumors that occur in women of reproductive age. Progesterone (P4) is a major hormone that promotes the ULs development and growth. P4 action in ULs is mediated mainly by its nuclear progesterone receptors (PGRs), although rapid non-genomic responses have also been observed. Data on the membrane progesterone receptors (mPRs) regulated signaling pathways in ULs in the available literature is still very limited. One of the essential characteristics of ULs is the excessive production of extracellular matrix (ECM). P4 has been shown to stimulate ECM production and collagen synthesis in ULs. Recent research demonstrated that, despite their benign nature, ULs may present with abnormal vasculature. P4 has been shown to regulate angiogenesis in ULs through the upregulation of vascular endothelial growth factor (VEGF) and by controlling the secretion of permeability factors. This review summarizes the key findings regarding the role of PGRs and mPRs in ULs, especially highlighting the potential ECM and angiogenesis modulation by P4. An increased understanding of this mechanistic role of nuclear and specifically mPRs in the biology of P4-modulated ECM and angiogenesis in the growth of ULs could turn out to be fundamental for developing effective targeted therapies for ULs., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The literature data regarding the risk of colorectal cancer (CRC) in the context of hormone therapy (HT), including both estrogen-progestogen combinations and estrogen alone, are inconclusive. The precise relationship underlying the action of progesterone (P4) and progesterone receptors in CRC has yet to be determined. We characterized the expression profiles of both nuclear and membrane progesterone receptors and their potential cofactors in CRC tissues. Additionally, we analyzed the P4 and NENF treatment effects on the cell proliferation and invasion of DLD-1 and HT-29 colorectal cancer cells. We observed a weak expression of the nuclear P4 receptor (PGR), but an abundant expression of the P4 receptor membrane component 1 (PGRMC1) and neuron-derived neurotrophic factor (NENF) in the CRC tissues. P4 treatment stimulated the proliferation of the DLD-1 and HT-29 CRC cells. The co-treatment of P4 and NENF significantly increased the invasiveness of the DLD-1 and HT-29 cells. A functional analysis revealed that these effects were dependent on PGRMC1. AN immunocytochemical analysis demonstrated a cytoplasmic co-localization of PGRMC1 and NENF in the CRC cells. Moreover, the concentration of serum NENF was significantly higher in CRC patients, and P4 treatment significantly increased the release of NENF in the DLD-1 cells. P4 or NENF treatment also significantly increased the IL-8 release in the DLD-1 cells. Our data may provide novel insights into the action of P4 and PGRMC1/NENF in CRC progression, where NENF may act as a potential PGRMC1 co-activator in non-classical P4 signaling. Furthermore, NENF, as a secreted protein, potentially could serve as a promising circulating biomarker candidate for distinguishing between colorectal cancer patients and healthy individuals, although large-scale extensive studies are needed to establish this.

Adenomyosis is a common gynaecological disease associated with the presence of endometrial lesions in the uterine myometrium. Estrogens have been proven to be the crucial hormones driving the growth of adenomyosis. Little is known about the distinct mechanisms of progesterone action in adenomyosis. Hence, in this study, we decided to characterize the expression of all nuclear and membrane estrogen and progesterone receptors. Additionally, as a functional investigation, we monitored prolactin production and cell proliferation after estradiol and progesterone treatments. We confirmed the presence of all nuclear and membrane estrogen and progesterone receptors in adenomyotic lesions at gene and protein levels. The expression of membrane progesterone receptors α and β (mPRα, mPRβ) as well as estrogen receptor β (ERβ) was upregulated in adenomyosis compared to normal myometrium. Estradiol significantly increased adenomyotic cell proliferation. Progesterone and cAMP upregulated prolactin secretion in adenomyosis in the same pattern as in the normal endometrium. In the present study, we showed the functional link between estradiol action and adenomyotic cell proliferation, as well as progesterone and prolactin production. Our findings provide novel insights into the sex steroid receptor expression pattern and potential regulated pathways in adenomyosis, suggesting that all receptors play an important role in adenomyosis pathophysiology.

The expression of the zona pellucida glycoprotein 3 (ZP3), originally thought to be specific for oocytes, was recently extended to ovarian, prostate, colorectal and lung cancers. Earlier successful ZP3 immunization of a transgenic mouse model carrying a ZP3 positive ovarian tumor emphasized the suitability of ZP3 for cancer immunotherapy. This study was carried out to determine whether any other normal tissues besides the ovary in healthy human and mouse tissues may express ZP3, considered important to exclude off-target effects of ZP3 cancer immunotherapy. Strong ZP3 expression was found in normal human and mouse testis. ZP3 protein and mRNA transcripts were localized in spermatogonia, spermatocytes and round and elongated spermatids of both human and mouse testis, as well as in a mouse spermatogonial cell line, but absent in testicular Sertoli, Leydig, spermatogonial stem and progenitor cells. All other normal human and mouse tissues were ZP3 negative. This surprising testicular ZP3 expression has implications for the development of ZP3 cancer immunotherapies, and it also alludes to the potential of using ZP3 as a target for the development of a male immunocontraceptive., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The selective progesterone receptor modulator mifepristone (MF) may act as a potent antiproliferative agent in different steroid-dependent cancers due to its strong antagonistic effect on the nuclear progesterone receptor (PGR). Hereby, we analyzed the effects of MF treatment on Leydig cell tumor (LCT) progression in a transgenic mouse model (inhibin-α promoter-driven SV40 T-antigen), as well as on LCT (BLTK-1 and mLTC-1) cell proliferation. MF significantly stimulated the proliferation of LCT in vitro. Similarly, a 1-mo MF or P4 treatment stimulated LCT tumor growth in vivo. Traceable/absent classical Pgr or nonclassical membrane PRs α, β, γ and Pgrmc2, but abundant membrane Pgrmc1 expression, was found in LCTs. MF did not activate glucocorticoid or androgen receptors in LCTs. Functional analysis showed that PGRMC1 is required for MF and P4 to stimulate the proliferation and invasiveness of LCTs. Accordingly, MF and P4 induced PGRMC1 translocation into the nucleus and thereby stimulated the release of TGFβ1 in LCT cells. MF and P4 treatments upregulated Tgfbr1 , Tgfbr2, and Alk1 expression and stimulated TGFβ1 release in LCT cells. Our findings provide novel mechanistic insights into the action of MF as a membrane PR agonist that promotes LCT growth through PGRMC1 and the alternative TGFβ1 signaling pathway.

Purpose: Exaggerated release of proinflammatory mediators during sepsis contributes to inadequate vasodilatation and depressed myocardial contractility, which lead to development of shock and circulatory collapse. The aim of the study was to evaluate the effect of IL-6 and aging on activation of intracellular signaling pathways in the myocardium induced by bacterial lipopolysaccharide (LPS) administration., Material/methods: LPS was injected intraperitoneally to male 3- and 24-month old mice with systemic IL-6 gene knock-out (IL-6KO) and the reference strain (WT). LPS was given intraperitoneally in single low (0.1 mg/kg) or high (10 mg/kg) dose, or in two doses (0.1 + 10 mg/kg) with 24-h delay. The expression and phosphorylation of STAT3, ERK1/2, Akt1/2/3 proteins in the left ventricular myocardium was evaluated after 24 h using Western blotting., Results: Low LPS dose induced higher STAT3 phosphorylation only in old IL-6KO mice, not affecting ERK1/2 and Akt1/2/3 phosphorylation in any group. High LPS dose upregulated STAT3 phosphorylation similarly in all groups, reduced ERK1/2 expression in young WT mice and upregulated Akt1/2/3 expression and phosphorylation in young IL-6KO mice. Pretreatment with low LPS dose attenuated phosphorylation of STAT3 in both old groups and phosphorylation of Akt1/2/3 in young IL-6KO group. Two-dose approach also significantly potentiated ERK1/2 phosphorylation in both old groups., Conclusions: Obtained results show that IL-6 deficiency alters the activity of intracellular signaling pathways: JAK/STAT in old and Akt in young LPS-treated mice. This may indicate that lack of IL-6 attenuates Akt-related cytoprotective effect of pretreatment with low LPS dose in young but not in aged animals., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2020 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Background: Recent clinical trials on ovarian cancer with mifepristone (MF) have failed, despite in vitro findings on its strong progesterone (P4) antagonist function., Methods: Ovarian cancer human and murine cell lines, cultured high-grade human primary epithelial ovarian cancer (HG-hOEC) cells and their explants; as well as in vivo transgenic mice possessing ovarian cancer were used to assess the molecular mechanism underlying mifepristone (MF) agonistic actions in ovarian cancer progression., Findings: Herein, we show that ovarian cancer cells express traceable/no nuclear P4 receptor (PGR), but abundantly P4 receptor membrane component 1 (PGRMC1). MF significantly stimulated ovarian cancer cell migration, proliferation and growth in vivo, and the translocation of PGRMC1 into the nucleus of cancer cells; the effects inhibited by PGRMC1 inhibitor. The beneficial antitumor effect of high-doses MF could not be achieved in human cancer tissue, and the low tissue concentrations achieved with the therapeutic doses only promoted the growth of ovarian cancers., Interpretation: Our results indicate that treatment of ovarian cancer with MF and P4 may induce similar adverse agonistic effects in the absence of classical nuclear PGRs in ovarian cancer. The blockage of PGRMC1 activity may provide a novel treatment strategy for ovarian cancer. FUND: This work was supported by grants from the National Science Centre, Poland (2013/09/N/NZ5/01831 to DP-T; 2012/05/B/NZ5/01867 to MC), Academy of Finland (254366 to NAR), Moikoinen Cancer Research Foundation (to NAR) and EU PARP Cluster grant (UDA-POIG.05.01.00-005/12-00/NCREMFP to SW)., (Copyright © 2019. Published by Elsevier B.V.)

Background: Interleukin 6 (IL-6) may be involved in regulation of cardiac lipid metabolism and mitochondrial function through its influence on peroxisome proliferator-activated receptors (PPARs). In this study we evaluated the impact of the physiological level of IL-6 on the expression of PPARα and PGC-1α in the heart and the effect of lack of this cytokine on high-fat diet (HFD) induced lipotoxicity., Methods: Male C57BL6/J wild type (WT) and IL-6 knock-out (IL-6KO) mice were used. 20 animals of each genotype were fed with HFD for 15-18weeks. Cardiac function was assessed using echocardiography and cardiomyocyte ultrastructure was examined using electron microscopy. QT-PCR and Western blotting were applied to estimate the expression of PPARα and PGC-1α at the transcriptional and protein levels., Results: At baseline WT and IL-6KO mice had similar size and function of the left ventricle. HFD induced similar left ventricular hypertrophic response in both groups without causing heart failure, but only WT animals had increased resting ejection fraction of the LV. Ultrastructure of HFD groups showed markers of lipotoxicity, that were more pronounced in IL-6KO group. In basal conditions IL-6KO animals had lower PPARα and similar PGC-1α expression as compared to WT. HFD induced downregulation of both PPARα and PGC-1α in WT animals, while in IL-6KO mice this effect was constrained., Conclusion: IL-6 is involved in basal regulation of PPARα and PGC-1α expression in cardiomyocytes. The lack of this cytokine promotes high-fat diet induced lipotoxicity but without overt manifestations of cardiac failure., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Myxomas are the most common non-invasive but life-threatening cardiac neoplasms due to obstruction of heart chambers and risk of embolism in a manner resembling thromboembolism as well. They can occasionally disseminate via their detached fragments into the bloodstream to seed and grow as secondary still benign tumors. In this study we evaluated morphological and clinical aspects of 14 ancient, degenerated left or right-sided cardiac atrial myxomas with expression of CD9 and CD63, which are found to contribute to platelet activation, aggregation and, as a result, intratumoral thrombosis or fragmentation. The appearance of tumors varied from sessile to polypoid revealing that a higher rate of endocardial thrombosis was associated with sessile compared to polypoid myxomas and left-sided tumors compared to right-sided ones in our study. In the general aspect of ancient calcifications, amorphous calcification with intra-tumor thrombosis was noted more frequently in sessile tumors, while well-formed osseous metaplasia was usually a feature of polypoid tumors. In our material osseous metaplasia did not coexist with massive thrombosis and was found in polypoid, pedunculated myxomas. Most importantly, CD9 overexpression was recorded in every studied myxoma and CD63 gave a weak reaction in myxoma cells.

Introduction: Astrocytic tumors are the most common primary brain tumors, but little is known about their etiology and prognostic factors. N-cadherin and beta-catenin are adhesive proteins, and are often overexpressed in many types of cancers, including breast or colorectal cancer, resulting in better prognosis. Connexin 43 is a gap junction protein involved in cell-cell signaling pathway taking part in the process of carcinogenesis. The aim of the study was to evaluate N-cadherin, beta-catenin and connexin 43 expression in astrocytic tumors of various grades., Materials and Methods: We examined 131 cases of astrocytic tumors, including 26 cases of diffuse astrocytoma (group I), 44 anaplasic astrocytomas (group II) and 61 glioblastoma cases (group III)--primary and secondary. To evaluate N-cadherin, beta-catenin and connexin 43 expression, we used immunohistochemical reaction with specific antibodies (Santa Cruz Biotechnology). The obtained results were correlated with clinical and morphological features., Results: Beta-catenin expression was observed in 69.3% of diffuse astrocytomas, 75% of anaplastic astrocytomas, and 82% of glioblastoma cases. N-cadherin expression was observed in 92.3% of diffuse astrocytomas, 90.1% of anaplastic astyrocytomas, and in all glioblastoma cases. Connexin 43 was observed in 76.9% of diffuse astrocytomas, and in all cases of anaplastic astrocytomas and glioblastomas. Beta-catenin expression was significant within the nucleus of neoplastic cells in groups I and II. In group III, staining was observed only in the cellular membranes. N-cadherin and connexin 43 expression was observed only in the cells' membranes. In glioblastomas, both primary and secondary, all protein expression was significant within the cells surrounding the necroses and blood vessels and weak or absent in the tumor's margins., Conclusion: Our study shows that beta-catenin nuclear expression in group of diffuse astrocytomas and anaplastic astrocytomas is evidence for transcriptional function of beta-catenin in those groups. Strong N-cadherin and connexin 43 expression in those groups may be evidence for their role in tumor formation and progression. However, in glioblastomas a very important role of all examined proteins is generating intracellular connections to facilitate the escape of tumor cells from the effects of hypoxia or their accumulation around the blood vessels rather than tumor invasion into the brain parenchyma.

Glaucoma is a result of increased intraocular pressure leading to damage to retinal ganglion cells and optic nerve axons. The aim of this study was to evaluate HIF-1 expression in optic nerve axons and retinal ganglion cells in 42 eyes enucleated because of complete glaucoma compared to eyes removed because of injury.The immunohistochemical reaction was done and specimens were examined under a light microscope. 57% of cases presented HIF-1 expression in the optic nerve axons, and 52.3% in the retinal ganglion cells. 20 out of 42(47.6%) cases were HIF-1 positive both in the optic nerve axons and in the retinal ganglion cells, and the staining was evident mostly in the nuclear and perinuclear area. Our present results indicate that HIF-1 expression in hypoxic conditions in glaucoma might be a very crucial stage in damage to retinal ganglion cells and optic nerve axons, and might be a successful target for the implementation of neuroprotective drugs.

Papillomas and squamous cell carcinomas are the most common conjunctival and eyelid lesions. The etiology is still unclear and recently human papillomavirus infection and p53 gene mutation have been taken into consideration. The aim of our study was the evaluation of HPV DNApresence and p53 gene mutation in 45 benign and 38 malignant squamous lesions of the conjunctiva and eyelid. For HPV detection PCR-RFLP and immunohistochemical reaction were used; for p53 gene mutation PCR-SSCP was used. Only 8.8% papillomas, 9.1% squamous cell cancers and 3.7% basal cell cancers (using PCR-RFLP method) and 26.6% papillomas, 7.4% squamous cell cancers and 9.1% basal cell cancers (using immunohisto-chemical reaction) were HPV positive. p53 gene mutation was evaluated in 24.4% papillomas, 54.5% squamous cell cancers and 22.2% basal cell cancers; most commonly in 6 and 7 exon. Human papillomavirus infection, opposite to p53 gene mutation, is not a significant etiological factor of the benign and malignant conjunctival and eyelid lesions development.