Результаты поиска

Potassium channel induction by the Ras/Raf signal transduction cascade.

p21ras plays a critical role in cell growth, differentiation, and oncogenic transformation. However, the final physiological effectors of p21ras-mediated signal transduction remain to be determined. We have used patch clamp electrophysiology, pharmacological agents, and transfection with specific Ras or Raf plasmids, to demonstrate that induction of a unique Ca(2+)-activated K+ channel in murine fibroblast cell lines depends on p21ras and its immediate downstream target, the Raf kinase. The importance of this channel in mitogenic signaling is further indicated by its induction in nontransforme

Trametinib in Patients With NF1-, GNAQ-, or GNA11-Mutant Tumors: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocols S1 and S2.

PURPOSE: NCI-MATCH is a precision medicine trial using genomic testing to allocate patients with advanced malignancies to targeted treatment subprotocols. This report combines two subprotocols evaluating trametinib, a MEK1/2 inhibitor, in patients with Neurofibromatosis 1 (NF1[S1] or GNA11/Q [S2]) altered tumors. METHODS: Eligible patients had tumors with deleterious inactivating NF1 or GNA11/Q mutations by the customized Oncomine AmpliSeq panel. Prior MEK inhibitor treatment was excluded. Glioblastomas (GBMs) were permitted, including malignancies associated with germline NF1 mutations (S1 o

Современные методы диагностики медицинских паразитов и артроподов

Обычные методы, такие, как микроскопия, используются для диагностики паразитических заболеваний и медицинских заболеваний, связанных с артроподами, на протяжении многих лет. Некоторые методы считаются золотыми. Однако их ограниченная чувствительность, специфичность и точность, а также потребность в дорогостоящих реагентах и высококвалифицированных технических специалистах являются критическими проблемами. В этой связи постоянно разрабатываются новые инструменты для уменьшения числа проблем. Недавно three Возникли самые современные методы: штрих-кодирование ДНК, геометрические морфометры и иску

Совпадение в полном тексте источника
… Discriminations using DNA barcoding technique of Culicidae mosquitoes, Psychodidae sandflies, Simuliidae black flies, and organisms in the class Arachnida, such as Buthidae scorpions, Ixodidae ticks, and Trombiculidae mites, have been reported [ 38 , 43 , 44 , 45 ]. … Two new species of Euscorpius (Scorpiones: Euscorpiidae) from Bulgaria, Serbia, and Greece Zootaxa 2014 3894 83 105 10.11646/zootaxa.3894.1.7 25544622 44. Ondrejicka D.A. Morey K.C. Hanner R.H. …

Modulation of voltage-dependent and inward rectifier potassium channels by 15-epi-lipoxin-A4 in activated murine macrophages: implications in innate immunity.

Potassium channels modulate macrophage physiology. Blockade of voltage-dependent potassium channels (Kv) by specific antagonists decreases macrophage cytokine production and inhibits proliferation. In the presence of aspirin, acetylated cyclooxygenase-2 loses the activity required to synthesize PGs but maintains the oxygenase activity to produce 15R-HETE from arachidonate. This intermediate product is transformed via 5-LOX into epimeric lipoxins, termed 15-epi-lipoxins (15-epi-lipoxin A4 [e-LXA4]). Kv have been proposed as anti-inflammatory targets. Therefore, we studied the effects of e-LXA4

Potent suppression of vascular smooth muscle cell migration and human neointimal hyperplasia by KV1.3 channel blockers.

AIM: The aim of the study was to determine the potential for K(V)1 potassium channel blockers as inhibitors of human neoinitimal hyperplasia. METHODS AND RESULTS: Blood vessels were obtained from patients or mice and studied in culture. Reverse transcriptase-polymerase chain reaction and immunocytochemistry were used to detect gene expression. Whole-cell patch-clamp, intracellular calcium measurement, cell migration assays, and organ culture were used to assess channel function. K(V)1.3 was unique among the K(V)1 channels in showing preserved and up-regulated expression when the vascular smoo

K(V)alpha1 channels in murine arterioles: differential cellular expression and regulation of diameter.

The primary objectives of this study were to reveal cell-specific expression patterns and functions of voltage-gated K(+) channel (K(V)alpha1) subunits in precapillary arterioles of the murine cerebral circulation. K(V)alpha1 were detected using peptide-specific antibodies in immunofluorescence and Western blotting assays. K(V)1.2 was localized almost exclusively to endothelial cells, whereas K(V)1.5 was discretely localized to the nerves and nerve terminals that innervate the arterioles. K(V)1.5 also localized specifically to arteriolar nerves in human pial membrane. K(V)1.5 was notable for i

Suppression of the rat microglia Kv1.3 current by src-family tyrosine kinases and oxygen/glucose deprivation.

Microglia activate following numerous acute insults to the brain, including oxygen/glucose deprivation (OGD), and both protein tyrosine kinases (PTKs) and K+ channels have been implicated in their activation. We identified Kv1.3 (voltage-gated potassium channel) protein in cultured rat microglia and confirmed that the native current is biophysically and pharmacologically similar to Kv1. 3. To explore whether src-family PTKs regulate the microglial Kv current, we first heterologously expressed Kv1.3 in a microglia-like cell line derived from neonatal rat brain (MLS-9). The resulting large Kv1.3

Adrenergic regulation of calcium-activated potassium current in cultured rabbit pigmented ciliary epithelial cells.

1. The effects of adrenergic agonists on K+ currents were studied in cultured rabbit pigmented ciliary epithelial (PCE) cells. 2. Outward K+ current (IK) was reduced by tetraethylammonium chloride, the Ca2+-activated K+ (K(Ca)) channel blocker iberiotoxin (IbTX), or Ca2+-free external Ringer solution. The calcium ionophore ionomycin increased an IbTX-sensitive IK in PCE cells. 3. The adrenergic agonists adrenaline and phenylephrine increased IK in PCE cells. The induced current was blocked by IbTX and the alpha1-antagonist prazosin, suggesting that adrenergic agonists activate IK(Ca) via alpha

Full-length and truncated Kv1.3 K+ channels are modulated by 5-HT1c receptor activation and independently by PKC.

In T-cells, the Shaker-related gene, Kv1.3 encodes the type n K+ channel, whereas the type l channel is a product of the Shaw. subfamily gene, Kv3.1. Both these genes are also expressed in the brain. We have used the Xenopus oocyte heterologous expression system to study the modulatory effects of serotonin (5-hydroxytryptamine, 5-HT) on both these cloned channels. In oocytes coexpressing the mouse 5-HT1c receptor and mouse Kv1.3 channel, addition of 100 nM 5-HT causes a complete and sustained suppression of Kv1.3 currents in approximately 20 min. In contrast, 5-HT has no effect on mouse Kv3.1

Новые тенденции в нанобиосистемах Змей-Веном-Лоадед: всеобъемлющий обзор.

Достижения в медицинской нанобиотехнологии в значительной степени способствовали применению ядов змеиных токсинов, облегчая разработку новых методов лечения токсинов, производимых животными. Огромное разнообразие видов змей и их ядовые сложности подчеркивают необходимость продолжения исследований. Этот обзор посвящен изучению интеграции яда змеиных ядов с наночастицами, с тем чтобы они могли использоваться в лечении человека в целях разработки методов лечения. Сложная смесь яда змей не только вызывает значительные патологические последствия, но и позволяет получить ценные знания для создания н

Совпадение в полном тексте источника
… Snake Venom Composition Venoms and/or poisons are used for predatory and defensive purposes and have evolved independently in a wide phylogenetic range of organisms, including snakes, spiders, scorpions, and jellyfish, among others [ 14 , 15 , 16 ]. … Development and characterization of a new carrier for vaccine delivery based on calcium-alginate nanoparticles: Safe immunoprotective approach against scorpion envenoming. Vaccine. 2016;34:2692–2699. doi: 10.1016/j.vaccine.2016.04.035. 82. Archer E., Torretti M., Madbouly S. …

CAR-T in relapsed refractory high-grade glioma and glioblastoma - who, what, when and how?

Recurrent high-grade gliomas have a dismal prognosis. This review article aimed to explore and help answer the questions about which group of patients would benefit from chimeric antigen receptor therapy (CAR-T) cell therapy in this setting, the timing of intervention and the therapeutic efficacy. CAR-T cell therapy involves the extraction of T-cells from patients, genetic modification of these cells to express chimeric antigen receptors on their cell surface, which are selectively targeted towards tumour-expressed antigens and a procedure of immune-depletion followed by re-introducing these e

Next-generation sequencing: advances and applications in cancer diagnosis.

Technological advances have led to the introduction of next-generation sequencing (NGS) platforms in cancer investigation. NGS allows massive parallel sequencing that affords maximal tumor genomic assessment. NGS approaches are different, and concern DNA and RNA analysis. DNA sequencing includes whole-genome, whole-exome, and targeted sequencing, which focuses on a selection of genes of interest for a specific disease. RNA sequencing facilitates the detection of alternative gene-spliced transcripts, posttranscriptional modifications, gene fusion, mutations/single-nucleotide polymorphisms, smal

Preferential expression and function of voltage-gated, O2-sensitive K+ channels in resistance pulmonary arteries explains regional heterogeneity in hypoxic pulmonary vasoconstriction: ionic diversity in smooth muscle cells.

Hypoxic pulmonary vasoconstriction (HPV) is initiated by inhibition of O2-sensitive, voltage-gated (Kv) channels in pulmonary arterial smooth muscle cells (PASMCs). Kv inhibition depolarizes membrane potential (E(M)), thereby activating Ca2+ influx via voltage-gated Ca2+ channels. HPV is weak in extrapulmonary, conduit pulmonary arteries (PA) and strong in precapillary resistance arteries. We hypothesized that regional heterogeneity in HPV reflects a longitudinal gradient in the function/expression of PASMC O2-sensitive Kv channels. In adult male Sprague Dawley rats, constrictions to hypoxia,

BeKm-1 is a HERG-specific toxin that shares the structure with ChTx but the mechanism of action with ErgTx1.

Peptide toxins with disulfide-stabilized structures have been used as molecular calipers to probe the outer vestibule structure of K channels. We want to apply this approach to the human ether-a-go-go-related gene (HERG) channel, whose outer vestibule is unique in structure and function among voltage-gated K channels. Our focus here is BeKm-1, a HERG-specific peptide toxin that can suppress HERG in the low nM concentration range. Although BeKm-1 shares the three-dimensional scaffold with the well-studied charybdotoxin, the two use different mechanisms in suppressing currents through their targ

K+ channels and the microglial respiratory burst.

Microglial activation following central nervous system damage or disease often culminates in a respiratory burst that is necessary for antimicrobial function, but, paradoxically, can damage bystander cells. We show that several K+ channels are expressed and play a role in the respiratory burst of cultured rat microglia. Three pharmacologically separable K+ currents had properties of Kv1.3 and the Ca2+/calmodulin-gated channels, SK2, SK3, and SK4. mRNA was detected for Kv1.3, Kv1.5, SK2, and/or SK3, and SK4. Protein was detected for Kv1.3, Kv1.5, and SK3 (selective SK2 and SK4 antibodies not av

Characterisation of K+ currents in the C8-B4 microglial cell line and their regulation by microglia activating stimuli.

Microglia are the intrinsic immune cells of the brain. As such, they are crucially involved in neuro-protection as well as neuro-degeneration. Their activation leads to the induction of cytokine and chemokine release, the production of reactive oxygen species and nitric oxide and an increased outward potassium conductance. In this study, we focus our interest on potassium currents and channels in the C8-B4 murine microglial cell line and compare them with those of primary cultured microglia from neo-natal mice. Using the whole cell patch-clamp technique, we have recorded prominent inward and o

Selective blocking of voltage-gated K+ channels improves experimental autoimmune encephalomyelitis and inhibits T cell activation.

Kaliotoxin (KTX), a blocker of voltage-gated potassium channels (Kv), is highly selective for Kv1.1 and Kv1.3. First, Kv1.3 is expressed by T lymphocytes. Blockers of Kv1.3 inhibit T lymphocyte activation. Second, Kv1.1 is found in paranodal regions of axons in the central nervous system. Kv blockers improve the impaired neuronal conduction of demyelinated axons in vitro and potentiate the synaptic transmission. Therefore, we investigated the therapeutic properties of KTX via its immunosuppressive and symptomatic neurological effects, using experimental autoimmune encephalomyelitis (EAE), an a

IGF-1 up-regulates K+ channels via PI3-kinase, PDK1 and SGK1.

Involvement of voltage-gated (Kv) potassium channels in IGF-1-induced proliferation of HEK293 cells was studied by patch-clamp, RT-PCR and FACS analysis. IGF-1 up-regulated outwardly rectifying whole-cell K+ current starting after 1 h of incubation and reaching a maximum after 4-6 h. The IGF-1-stimulated current was voltage-gated with an activation threshold of -30 mV to -40 mV, a half-maximal activation at +5.3+/-1.8 mV, and time constants for activation and inactivation of 4.5+/-0.4 ms and 43.5+/-5.6 ms ( n=10), respectively. The current was inhibited by TEA, margatoxin, agitoxin-2 and stich

CAR-T cell therapy for the treatment of adult high-grade gliomas.

Treatment for malignant primary brain tumors, including glioblastoma, remains a significant challenge despite advances in therapy. CAR-T cell immunotherapy represents a promising alternative to conventional treatments. This review discusses the landscape of clinical trials for CAR-T cell therapy targeting brain tumors, highlighting key advancements like novel target antigens and combinatorial strategies designed to address tumor heterogeneity and immunosuppression, with the goal of improving outcomes for patients with these aggressive cancers.

Design and characterization of a highly selective peptide inhibitor of the small conductance calcium-activated K+ channel, SkCa2.

Apamin-sensitive small conductance calcium-activated potassium channels (SKCa1-3) mediate the slow afterhyperpolarization in neurons, but the molecular identity of the channel has not been defined because of the lack of specific inhibitors. Here we describe the structure-based design of a selective inhibitor of SKCa2. Leiurotoxin I (Lei) and PO5, peptide toxins that share the RXCQ motif, potently blocked human SKCa2 and SKCa3 but not SKCa1, whereas maurotoxin, Pi1, Tskappa, and PO1 were ineffective. Lei blocked these channels more potently than PO5 because of the presence of Ala(1), Phe(2), an