Chrysin and its potential antineoplastic effect

In 2012, in Europe, there were noticed over 3 million new cases of cancer and 1.75 million of deaths from cancer. Numerous anticancer agents are cytotoxic, can damage normal cells, and they can cause serious side effects. Currently, natural and non-toxic agents are being sought that reduce the cost of therapy, are more effective and targeted, and do not damage healthy cells. Chrysin which belong to flavonoids family as natural substance, has multiple anticancer activities. It has been reported that chrysin can induce apoptosis in tumour cells by different mechanism. In our work we demonstrated the potential use of chrysin in gastrointestinal, breast, cervical, and lung cancer. In conclusion it is proven that chrysin or combination of chrysin with other related drugs can effectively improve the effectiveness of anticancer therapy. Furthermore, new agents, such as nanoparticles, may show greater efficacy, and better targeting, hence, less side effects on healthy cells. Based on these results, nanochrysin it offers as new and effective drug delivery system. Moreover, it has been reported that chrysin is a potential antitumor but also an adjuvant agent that can be used in combination with other antimetastatic substances to reduce tumor metastasis. DOI: http://dx.doi.org/10.5281/zenodo.84447

Major regulators of microRNAs biogenesis Dicer and Drosha are down-regulated in endometrial cancer

Alterations in microRNAs expression have been proposed to play role in endometrial cancer pathogenesis. Dicer and Drosha are main regulators of microRNA biogenesis and deregulation of their expression has been indicated as a possible cause of microRNAs alterations observed in various cancers. The objective of this study was to investigate Dicer and Drosha genes expression in endometrial cancer and to analyze the impact of clinicopathological characteristics on their expression. Fresh tissue samples were collected from 44 patients (26 endometroid endometrial carcinoma and 18 controls). Clinical and pathological data were acquired from medical documentation. Dicer and Drosha genes expressions were assessed by qRT-PCR using validated reference genes. Dicer and Drosha expression levels were significantly lower in endometrial cancer samples comparing to controls. Dicer was down-regulated by the factor of 1.54 (p = 0.009) and Drosha gene mean expression value was 1.4 times lower in endometrial cancer group versus control group (p = 0.008). Down-regulation of Dicer significantly correlated with decreased expression of Drosha (coefficient value 0.75). Decreased expression of Drosha correlated with higher histological grade and was influenced by BMI. Lower Dicer expression was found in nulli- and uniparous females comparing to multiparous individuals (p = 0.002). Neither the FIGO stage nor the menstrual status had significant influence on the expression of studied genes. This study revealed for the first time that expression alterations of main regulators of microRNAs biogenesis are present in endometrial cancer tissue and could be potentially responsible for altered microRNAs profiles observed in this malignancy

Skuteczność ruksolitynibu w leczeniu chorych na mielofibrozę z chorobami współistniejącymi

Myelofibrosis (MF) is a heterogenous Philadelphia-myeloproliferative neoplasm that is characterized by bone marrow fibrosis and impaired hematopoiesis. Clinical hallmarks of MF are increased splenomegaly, cytopenias and general symptoms. Deregulation of JAK–STAT signaling pathway plays a key role in the pathogenesis of MF. Ruxolitinib is a selective and oral JAK1/JAK2 inhibitor that in clinical trials demonstrated significant efficacy in the reduction of clinical symptoms, improved the quality of life and increased overall survival of patients with MF.Mielofibroza (MF) jest heterogennym nowotworem układu krwiotwórczego, cechującym się brakiem chromosomu Filadelfia i włóknieniem szpiku oraz wynikającym z tego upośledzeniem hematopoezy. Objawami klinicznymi MF są powiększenie śledziony, cytopenie oraz objawy ogólne. W patogenezie MF szczególną rolę odgrywają zaburzenia szlaku JAK–STAT. Ruksolitynib jest selektywnym, doustnym inhibitorem JAK1/JAK2, który w badaniach klinicznych wykazał istotną skuteczność w zmniejszeniu objawów klinicznych, poprawie jakości życia oraz wydłużeniu całkowitego przeżycia chorych na MF

Choroba Alzheimera – rola badań immunohistochemicznych w diagnostyce choroby = Alzheimer's disease - the role of immunohistochemistry in the diagnosis of disease

Cichacz-Kwiatkowska Beata, Sekita-Krzak Joanna, Kot-Bakiera Katarzyna, Jodłowska-Jędrych Barbara, Wawryk-Gawda Ewelina. Choroba Alzheimera – rola badań immunohistochemicznych w diagnostyce choroby = Alzheimer's disease - the role of immunohistochemistry in the diagnosis of disease. Journal of Education, Health and Sport. 2016;6(2):122-137. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.45939 http://ojs.ukw.edu.pl/index.php/johs/article/view/3380 https://pbn.nauka.gov.pl/works/713623 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 755 (23.12.2015). 755 Journal of Education, Health and Sport eISSN 2391-8306 7 © The Author (s) 2016; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 01.01.2016. Revised 12.01.2016. Accepted: 31.01.2016. Choroba Alzheimera – rola badań immunohistochemicznych w diagnostyce choroby Alzheimer's disease - the role of immunohistochemistry in the diagnosis of disease Beata Cichacz-Kwiatkowska1ABD, Joanna Sekita-Krzak1ABD, Katarzyna Kot‑Bakiera1ABD, Barbara Jodłowska-Jędrych1ABD, Ewelina Wawryk‑Gawda1ABD 1Katedra i Zakład Histologii i Embriologii z Pracownią Cytologii Doświadczalnej, Uniwersytet Medyczny, Lublin, Polska Authors’ Contribution: A Study Design B Data Collection C Statistical Analysis D Manuscript Preparation E Funds Collection Słowa kluczowe: badania immunohistochemiczne, choroba Alzheimera, wewnątrzkomórkowe zwyrodnienia włókienkowe typu Alzheimera, białkowe prekursor amyloidu. Key words: immunohistochemistry, Alzheimer's disease, neurofibrillary tangles, amyloid precursor protein. Glosariusz: Choroba Alzheimera – najczęstsza postać otępienia, nieuleczalna i postępująca choroba neurodegeneracyjna, po raz pierwszy opisana w 1906 przez Alois Alzheimer [1] Glossary: Alzheimer's disease (AD), also known as Alzheimer disease, the most common form of dementia, progressive neurodegenerative disease, first described by Alois Alzheimer in 1906 [1] Streszczenie Choroba Alzheimera jest przewlekłą i postępującą chorobą neurodegeneracyjną, będącą zarazem najczęstszą przyczyną zespołu otępiennego. Skutki tej choroby dotykają zarówno samego pacjenta i jego otoczenie, przybierając wymiar zarówno społeczny jak i ekonomiczny. Częstość występowania otępienia towarzyszącego chorobie Alzheimera podwaja się co 4,5 roku u osób po 65. roku życia. U podłoża tego schorzenia leży zróżnicowana grupa zaburzeń związanych ze starzeniem się organizmu oraz interakcjami genetycznymi i środowiskowymi. Procesy neurodegeneracyjne obserwowane w przebiegu choroby Alzheimera prowadzą do upośledzenia morfologicznego i fizjologicznego neuronów oraz w konsekwencji ich śmierci. Doprowadza to bezpośrednio do upośledzenia kontroli poznawczej. W zmienionej patologicznie tkance nerwowej chorych stwierdzono obecność nieprawidłowych struktur, takich jak blaszki amyloidowe i zwyrodnienia włókienkowe (splątki neurofibrylarne). Sformułowano wiele hipotez starających się wyjaśnić procesy prowadzące do neurodegeneracji, najczęściej wymieniana jest teoria kaskady amyloidowej. Metody immunohistochemiczne pozwalają na wykrycie, zlokalizowanie i oznaczenie zmian neurodegeneracyjnych związanych z chorobą Alzheimera. Wykorzystywane są tutaj zarówno przeciwciała poli- jak i monoklonalne, a same badania charakteryzują się dużą czułością i swoistością. Summary Alzheimer's disease is a chronic, progressive disease, which has been classified as a most frequent causes of dementia in the elderly population. The consequences of this disease affects the patient and his family and have a social and economic dimension. In the population over 65 years of age the incidence of dementias accompanying Alzheimer's disease doubles every 4.5 years. This disease is caused by a diverse group of genetic and environmental disorders associated with aging of the organism. Neurodegenerative processes seen during the Alzheimer's Disease result in impairment of neurons morphological and physiological functions causing their death. This leads directly to the impairment of patients cognitive functions. In the pathologically altered nerve tissue the presence of abnormal structures such as amyloid plaques and fibrillar degeneration (neurofibrillary tangles) is revealed. Many hypotheses have been formulated trying to explain the processes leading to neurodegeneration, and the most often mentioned is the amyloid cascade theory. Immunohistochemistry can detect, locate and mark the changes related to the Alzheimer's disease neurodegeneration. They are used here both poly- and monoclonal antibodies, and the same tests are highly sensitive and specific

Expression of caspase 9 and p53 in uterine leiomyosarcomas

Uterine sarcomas are heterogeneous malignancies, both clinically and histologically. The process of oncogenesis depends on gene mutations and uncontrolled mitotic cell division that is promoted by blocking pathways of apoptosis. Caspase 9 and p53 protein play an important role in the process of cell apoptosis. Objectives: The aim of the study was to assess the expression of selected apoptosis proteins (caspase 9 and p53) using immunohistochemistry. Material and methods: A total of 28 tissue samples diagnosed in postoperative histopathological examination as leiomyosarcoma were tested. Twenty eight samples of leiomyomas were used as the control group. Colorful reactions with appropriate antibodies were performed to assess the expression of caspase 9 and p53. From every section 5 fields on view were chosen, in each one 100 cells were assessed using 400x magnification. T-Student parametric test and U Mann-Whitney test were used for statistical analysis. Results: Expression of caspase 9 was significantly lower (pMięsaki macicy są niejednorodną grupą nowotworow zarowno pod względem klinicznym jak i histologicznym. Proces onkogenezy związany z mutacją genow skutkuje nadmierną proliferacją oraz niekontrolowanym podziałem mitotycznym komórek poprzez blokowanie szlaków apoptozy. Kaspaza 9 oraz białko p53 odgrywają istotną rolę w procesie zaprogramowanej śmierci komórki. Cel pracy: Celem pracy była ocena immunohistochemiczna ekspresji kaspazy 9 oraz białka p53 w mięsakach macicy. Materiał i metody: Ocenie poddano 28 preparatów z rozpoznaniem histopatologicznym leiomyosarcoma uteri. Grupę kontrolną stanowiły tkanki mięśniaków macicy (n=28). Po wywołaniu reakcji barwnej przy użyciu przeciwciał przeciwko kaspazie 9 i p53, oceniano 100 komorek w polu widzenia o powiększeniu 400x, w obrębie 5 pol. Do analizy statystycznej wynikow zastosowano test parametryczny t-Studenta oraz U Manna-Whitneya. Wyniki: Ekspresja kaspazy 9 była istotnie statystycznie niższa (

Intrinsic Apoptosis Pathway in Fallopian Tube Epithelial Cells Induced by Cladribine

Cladribine is a purine nucleoside analog which initiates the apoptotic mechanism within cells. Moreover, the available data confirms that cladribine, with the participation of the p53 protein, as well as the proapoptotic proteins from the Bcl-2 family, also induces the activation of the intrinsic apoptosis pathway. However, while there has been a lot of research devoted to the effect of cladribine on lymphatic system cells, little is known about the impact of cladribine on the reproductive system. The aim of our study was to evaluate apoptosis in oviduct epithelial cells sourced from 15 different female rats. In so doing, the sections were stained with caspases 3, 9, and 8. Results suggest that cladribine also induces apoptosis in the oviduct epithelial cells by way of the intrinsic pathway. Indeed, the discontinuing of the administration of cladribine leads to a reduction in the amount of apoptotic cells in the oviduct epithelium

High doses of medroxyprogesterone as the cause of disappearance of adherence of the zona pellucida to an oocyte

The zona pellucida (ZP) is an external glycoprotein membrane of oocytes of mammals and embryos in the early stage of their development. ZP first appears in growing ovarian follicles as an extracellular substance between the oocyte and granular cells. The zona pellucid markedly affects the development and maturation of the oocyte. The morphology of the ZP-oocyte complex allows a more precise determination of the oocyte maturity. According to numerous experimental studies, ZP is essential for preimplantation embryonic development of humans and other mammals. It prevents dispersion of blastomeres and enhances their mutual interactions. ZP is a dynamic structure responsible for the provision of nutrients to early forms of oocytes in mammals. The aim of the present study was untrastructural evaluation of the ZP-oocyte contact during inhibited ovulation. Female white rats (Wistar strain) received a suspension of medroxyprogesterone acetate (MPA) in incremental intramuscular bolus doses of 3.7 mg (therapeutic dose), 7.4 mg and 11.1 mg. The animals were decapitated 5 days after the administration of MPA. Ovarian sections were evaluated under a transmission electron microscope (TEM) Zeiss EM 900. Morphometric analysis of ZP was conducted using the cell imaging system by Olympus. In females exposed to therapeutic doses of MPA, ZP showed the structure of granular-fibrous reticulum of a medium electron density with single cytoplasmic processes originating from the surrounding structures. The oocyte cell membrane generated single, delicate processes directed toward ZP. Microvilli of the oocyte were short and thin. In the group receiving 7.4 mg of MPA, ZP had the structure of a delicate, loose granular-fibrous reticulum, and the oocyte cell membrane generated single microvilli directed toward ZP. In both those groups, the close ZP-oocyte contact was observed. Otherwise, in the group exposed to the highest MPA doses (11.1 mg), thicker and more numerous oocyte microvilli were found, which did not penetrate ZP matrix. They were dense, irregularly separated contour, forming a barrier between ZP and oocyte. The present findings are likely to suggest that MPA has inhibiting effects on the synthesis of binding proteins and causes the loss of the oocyte contact with ZP

Does administration of non-steroidal anti-inflammatory drug determine morphological changes in adrenal cortex: ultrastructural studies

Rofecoxib (Vioxx© made by Merck Sharp & Dohme, the USA) is a non-steroidal anti-inflammatory drug which belongs to the group of selective inhibitors of cyclooxygenasis-2, i.e., coxibs. Rofecoxib was first registered in the USA, in May 1999. Since then the drug was received by millions of patients. Drugs of this group were expected to exhibit increased therapeutic action. Additionally, there were expectations concerning possibilities of their application, at least as auxiliary drugs, in neoplastic therpy due to intensifying of apoptosis. In connection with the withdrawal of Vioxx© (rofecoxib) from pharmaceutical market, attempts were made to conduct electron-microscopic evaluation of cortical part of the adrenal gland in preparations obtained from animals under influence of the drug. Every morning animals from the experimental group (15 rats) received rofecoxib (suspension in physiological saline)—non-steroidal anti-inflammatory drug (Vioxx©, Merck Sharp and Dohme, the USA), through an intragastric tube in the dose of 1.25 mg during 8 weeks. In the evaluated material, there was found a greater number of secretory vacuoles and large, containing cholesterol and other lipids as well as generated glucocorticoids, lipid drops in cytoplasm containing prominent endoplasmic reticulum. There were also found cells with cytoplasm of smaller density—especially in apical and basal parts of cells. Mitochondria occasionally demonstrated features of delicate swelling. The observed changes, which occurred on cellular level with application of large doses of the drug, result from mobilization of adaptation mechanisms of the organism