WDR5 inhibition halts metastasis dissemination by repressing the mesenchymal phenotype of breast cancer cells

Background: Development of metastases and drug resistance are still a challenge for a successful systemic treatment in breast cancer (BC) patients. One of the mechanisms that confer metastatic properties to the cell relies in the epithelial-to-mesenchymal transition (EMT). Moreover, both EMT and metastasis are partly modulated through epigenetic mechanisms, by repression or induction of specific related genes. Methods: We applied shRNAs and drug targeting approaches in BC cell lines and metastatic patient-derived xenograft (PDX) models to inhibit WDR5, the core subunit of histone H3 K4 methyltransferase complexes, and evaluate its role in metastasis regulation. Result: We report that WDR5 is crucial in regulating tumorigenesis and metastasis spreading during BC progression. In particular, WDR5 loss reduces the metastatic properties of the cells by reverting the mesenchymal phenotype of triple negative- and luminal B-derived cells, thus inducing an epithelial trait. We also suggest that this regulation is mediated by TGF\u3b21, implying a prominent role of WDR5 in driving EMT through TGF\u3b21 activation. Moreover, such EMT reversion can be induced by drug targeting of WDR5 as well, leading to BC cell sensitization to chemotherapy and enhancement of paclitaxel-dependent effects. Conclusions: We suggest that WDR5 inhibition could be a promising pharmacologic approach to reduce cell migration, revert EMT, and block metastasis formation in BC, thus overcoming resistance to standard treatments

Study of neuroprotective and insulinotropic activities of hydroponic Teucrium polium L in condition ovariectomy

The increased interest to the neuroprotective medical plants is caused by modulator influence of plant flavonoids on the functioning of synaptic mechanism. The aim of present study was the electrophysiological and morphohistochemical study of neuroprotective effectivity of Teucrium polium in condition of neurodegeneration induced by ovariectomy (OVX). Teucrium polium Lwas cultivated in open-air hydroponics for the purpose of enrichment of chemical composition by flavonoids and phenilglycosides. The extracellular registration of spiking activity of hippocampal single neurons by high-frequency stimulation of entorhinal cortex after 6 weeks ofbilateral ovariectomy (OVX), detected failures of excitatory and inhibitory responses of norm. Also it showed a deficit of neurotransmission and disturbance of synaptic transmission by sharp increase of areactive units. Intramuscular injection of Teucrium polium(20 mg/kg, during 3 weeks), promotes the reorganization of neuronal circuitries of cortex-hippocampus, starting from 3 week after OVX, by modulation of anomalous synaptic activity, according tocriteria of intensity of excitatory and inhibitory responses, as well as the balance of areactive and reactive units. Morphological and histochemical studypoints to neuroprotective effectivity of Teucrium polium in condition of OVX according to the positive changes in the structural properties of neurons and high phosphatase activity inall hippocampal regions, that, in general, defines the cellular survival. Teucrium poliumin the conditions of ОVХshows insulinotropic activity bringing the glucose level in the blood to the initial value

Magneto-absorption in cylindrical quantum dots

The absorption of light in an ensemble of non-interacting cylindrical quantum dots in the presence of a magnetic field is discussed using a model consisting of dots with rectangular infinitely-high potential barriers. The ensemble's absorption coefficient is calculated – as well as the threshold frequency of absorption – as a function of the applied magnetic field and the quantum dot size. Theoretical results are compared with experimental data on magneto-luminescence in an In0.53Ga0.47As/InP cylindrical quantum dot system. In addition, using a perturbation theory framework, the influence of excitonic effects on the behaviour of the electron-hole energetic spectrum of said system is discussed

Дослідження нейропротекторної та інсулінотропної активності гідропонічного Teucrіum polіum L за умов оваріектомії.

The increased interest to the neuroprotective medical plants is caused by modulator influence of plant flavonoids on the functioning of synaptic mechanism. The aim of present study was the electrophysiological and morphohistochemical study of neuroprotective effectivity of Teucrium polium in condition of neurodegeneration induced by ovariectomy (OVX). Teucrium polium L was cultivated in open-air hydroponics for the purpose of enrichment of chemical composition by flavonoids and phenilglycosides. The extracellular registration of spiking activity of hippocampal single neurons by high-frequency stimulation of entorhinal cortex after 6 weeks of bilateral ovariectomy (OVX), detected failures of excitatory and inhibitory responses of norm. Also it showed a deficit of neurotransmission and disturbance of synaptic transmission by sharp increase of areactive units. Intramuscular injection of Teucrium polium (20 mg/kg, during 3 weeks), promotes the reorganization of neuronal circuitries of cortex-hippocampus, starting from 3 week after OVX, by modulation of anomalous synaptic activity, according to criteria of intensity of excitatory and inhibitory responses, as well as the balance of areactive and reactive units. Morphological and histochemical study points to neuroprotective effectivity of Teucrium polium in condition of OVX according to the positive changes in the structural properties of neurons and high phosphatase activity in all hippocampal regions, that, in general, defines the cellular survival. Teucrium polium in the conditions of ОVХ shows insulinotropic activity bringing the glucose level in the blood to the initial value.Возросший интерес к нейропротекторным лекарственнным растениям обусловлен модуляторным воздействием растительных флавоноидов на функционирование синаптического аппарата. Цель исследования – электрофизиологическое и морфогистохимическое изучение нейропротекторной эффективности Teucrium polium L в условиях нейродегенерации, индуцированной двусторонним удалением яичников (овариэктомия – OВX). Для обогащения химического состава флавоноидами и фенолгликозидами Teucrium polium L (Дубровник беловойлочный) выращивали в открытой гидропонике. Экстраклеточной регистрацией спайковой активности единичных нейронов гиппокампа при стимуляции энторинальной коры у крыс спустя 6 недель после OВX выявлены нарушения существующего в норме баланса возбудительных и ингибиторных ответов, а также дефицит нейромедиации в виде резкого увеличения числа ареактивных нейрональных единиц. В/м инъекция Teucrium polium, начиная с 3-ей недели после OВX, способствует реорганизации нейронных цепей кора-гиппокамп модулированием аномальной синаптической активности – согласно критериям интенсивности возбудительных и ингибиторных ответов, а также баланса ареактивных и реактивных единиц. Морфогистохимическое исследование указывает на нейропротекторную эффективность Teucrium polium в условиях OВX согласно положительным изменениям структурных свойств нейронов и высокой фосфатазной активности во всех полях гиппакампа, в целом определяющей клеточное выживание. Teucrium polium в условиях OВX проявляет инсулинотропную активность, приближая уровень глюкозы в крови до исходного значения.Зростаючий інтерес до нейропротекторних лікарських рослин обумовлений модуляторним впливом рослинних флавоноїдів на функціонування синаптичного апарату. Мета дослідження – електрофізіологічне та морфогістохімічне вивчення нейропротекторної ефективності Teucrіum polіum L за умов нейродегенерації, яка індукована двобічним видаленням яєчників (оваріектомія - OВX). Для збагачення хімічного складу флавоноїдами та фенолглікозидами Teucrіum polіum L (Дубровник біловойлочний) вирощували у відкритій гідропоніці. Екстраклітинною реєстрацією спайкової активності одиничних нейронів гіпокампа при стимуляції енторинальної кори у щурів через 6 тижнів після OВХ виявлені порушення існуючого в нормі балансу збуджувальних та інгібованих відповідей, а також дефіцит нейромедиації у вигляді різкого збільшення числа ареактивних нейрональних одиниць. В/м ін'єкція Teucrіum polіum, починаючи з 3-го тижня після OВX, сприяє реорганізації нейронних ланцюгів кора-гіпокамп модулюванням аномальної синаптичної  активності – відповідно до критеріїв інтенсивності збуджувальних та інгібованих відповідей, а також балансу ареактивних та реактивних одиниць. Морфогістохімічне дослідження вказує на нейропротекторну ефективність Teucrіum polіum за умов OВX відповідно до позитивних змін структурних властивостей нейронів і високої фосфатазної активності у всіх полях гіпокампу, що в цілому визначає клітинне виживання. Teucrіum polіum за умов OВX виявляє інсулінотропну активність, наближаючи рівень глюкози в крові до вихідного значення

Neuroprotective action of proline-rich polypeptide-1 in β-amyloid induced neurodegeneration in rats

Original article can be found at: http://www.sciencedirect.com/ Copyright Elsevier [Full text of this article is not available in the UHRA]It is recognized that the main trigger of Alzheimer disease related neurodegeneration is β-amyloid peptide, which subsequently generates different metabolic disorders in neuron and finally leads to neuronal death. Several biologically active products were tested as neuroprotectors, but only few of them demonstrated any efficiency.Proline-rich polypeptide-1 was tested as a neuroprotective agent on Aβ25-35 animal model of Alzheimer disease. Biochemical analysis (determination of spectrum of neuroactive amino acids, such as glutamate, gamma-aminobutyric acid, glycine, aspartate and taurine), as well as behavioral, electrophysiological and morphological studies were performed to reveal the neuroprotective potential of proline-rich polypeptide in rats.Based on the results of our study it can be concluded that proline-rich polypeptide-1 has a potential to be one of the effective preventive or therapeutic agents against neurodegenerative disorders, such as Alzheimer disease.Peer reviewe

Cerebrovascular and Neuroprotective Effects of Adamantane Derivative

Objectives. The influence of 5-hydroxyadamantane-2-on was studied on the rats’ brain blood flow and on morphological state of brain tissue under the condition of brain ischemia. The interaction of the substance with NMDA receptors was also studied. Methods. Study has been implemented using the methods of local blood flow registration by laser flowmeter, [3H]-MK-801binding, and morphological examination of the brain tissue. We used the models of global transient ischemia of the brain, occlusion of middle cerebral artery, and hypergravity ischemia of the brain. Results. Unlike memantine, antagonist of glutamatergic receptors, the 5-hydroxyadamantane-2-on does not block NMDA receptors but enhances the cerebral blood flow of rats with brain ischemia. This effect is eliminated by bicuculline. Under conditions of permanent occlusion of middle cerebral artery, 5-hydroxyadamantane-2-on has recovered compensatory regeneration in neural cells, axons, and glial cells, and the number of microcirculatory vessels was increased. 5-Hydroxyadamantane-2-on was increasing the survival rate of animals with hypergravity ischemia. Conclusions. 5-Hydroxyadamantane-2-on, an adamantane derivative, which is not NMDA receptors antagonist, demonstrates significant cerebrovascular and neuroprotective activity in conditions of brain ischemia. Presumably, the GABA-ergic system of brain vessels is involved in mechanisms of cerebrovascular and neuroprotective activity of 5-hydroxyadamantane-2-on