Результаты поиска

Repurposing nirogacestat, a gamma secretase enzyme inhibitor in desmoid tumors.

The gamma secretase (GS) enzyme controls cell-cell adhesion, neural stem cell proliferation, neo-angiogenesis, spinal maturation, and metabolism of amyloid precursor proteins (APP). Pathological production of abnormal amyloid-beta isoforms and senile plaques serves as the basis for pathogenesis of Alzheimer's disease (AD). GS enzyme inhibitors such as semagacestat and avagacestat were explored in AD but the studies were paused because of adverse events attributed to their influence on the Notch pathway.Crosstalk between Notch and Wnt signaling pathways created a potential role for GS inhibitor

Совпадение в полном тексте источника
… A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions. Embo J. 2002. Apr 15;21(8):1948–1956. doi: 10.1093/emboj/21.8.1948 13. …

Иммунитет в нейромодуляции: исследование нейронных и иммунных путей в расстройствах мозга.

Иммунитет четко регулирует функцию мозга. Она непосредственно участвует в патологических процессах таких нейродегенеративных заболеваний, как болезнь Паркинсона и Альцгеймера, посттравматические заболевания, множественный склероз, травма головного мозга и психические расстройства (большое расстройство организма, серьезное депрессивное расстройство (МДС), расстройства тревожности, расстройства психоза и шизофрения, а также расстройства нервного развития (НРД). Нейромодулирование в настоящее время является одной из ведущих терапевтических стратегий лечения этих расстройств, однако пока мало что

Plasma microRNA profiles: identification of miR-25 as a novel diagnostic and monitoring biomarker in oesophageal squamous cell carcinoma.

BackgroundRecent studies have demonstrated that microRNAs are stably detectable in plasma/serum because of their binding to specific proteins or being packaged in secretory particles. This study was designed to detect novel microRNAs in plasma for cancer detection and monitoring using microRNA array-based approaches in oesophageal squamous cell carcinoma (ESCC) patients.MethodsThrough the integration of two Toray 3D-Gene microRNA array-based approaches to compare plasma microRNA levels between ESCC patients and healthy volunteers and between preoperative and postoperative ESCC patients, we ide

Diagnosis and treatment of multisystem amyloidosis associated with SGPL1 mutation: A case report and review of the literature.

RATIONALE: Amyloidosis is a rare, clinically heterogeneous disease, which makes its diagnosis difficult. The relationship between amyloidosis and gene mutations is insufficiently understood. We report a case of sphingosine-1-phosphate lyase 1 (SGPL1) mutation-related amyloidosis, and review the related literature. PATIENT CONCERNS: A 53-year-old man was admitted to our hospital with a 5-month history of renal dysfunction and abdominal distension, aggravated since 2 days. Five months ago, the patient was diagnosed with nephrotic syndrome, with liver dysfunction and abdominal distension. His sy

Integrated Pleiotropic Gene Set Unveils Comorbidity Insights across Digestive Cancers and Other Diseases.

Comorbidities are prevalent in digestive cancers, intensifying patient discomfort and complicating prognosis. Identifying potential comorbidities and investigating their genetic connections in a systemic manner prove to be instrumental in averting additional health challenges during digestive cancer management. Here, we investigated 150 diseases across 18 categories by collecting and integrating various factors related to disease comorbidity, such as disease-associated SNPs or genes from sources like MalaCards, GWAS Catalog and UK Biobank. Through this extensive analysis, we have established a

Совпадение в полном тексте источника
… CTNNB1 is part of a complex of proteins that constitute adherens junctions, essential for the formation and maintenance of epithelial cell layers by regulating cell growth and adhesion. It is a driver gene in stomach cancer [ 44 ]. …

Липидированные мезофорные наночастицы, нагруженные тимокиноном, в качестве нового метода лечения аутоиммунного энцефаломиелита у крыс.

AIMS: Пересечение мозгового барьера (BBB) по-прежнему является серьезной проблемой для доставки терапевтических агентов в центральную нервную систему. Цель этого исследования состояла в том, чтобы оценить потенциал новых наноформуляционных силикатных силиканочастиц (MSN), покрытых липидным двуслойным слоем (LB), с тем чтобы повысить уровень доставки и потенциальное ремиелионирующее воздействие тимокинона (TQ). МЕТОДЫ: Составы характеризовались микроскопией передачи электронов и динамическим рассеиванием света для определения потенциала зета и размера частиц. Экспериментальная аутоиммунная энце

Stabilization of DEPTOR sensitizes hypopharyngeal cancer to radiotherapy via targeting degradation.

The use of radiotherapy for hypopharyngeal cancer (HC) treatment is increasing, and it is currently the primary treatment option for this cancer. However, radioresistance occurs in a proportion of patients. Here, we found that radiation increased proteasomal gene expression and that proteasome assembly was dependent on the induction of transcription factor NRF1 in HC. Through screening assays, we identified a mechanism by which proteasome-mediated degradation of DEP domain-containing mTOR-interacting protein (DEPTOR) contributes to the elevation of mTORC1 signaling after radiation. Therefore,

Совпадение в полном тексте источника
… Mitofusin-2 stabilizes adherens junctions and suppresses endothelial inflammation via modulation of β-catenin signaling Nat. Commun. 12 2021 2736 10.1038/s41467-021-23047-6 33980844 PMC8115264 44 Naumann P. Liermann J. Fortunato F. Schmid T.E. Weber K.J. Debus J. Combs S.E. …

Liposomes for the Treatment of Brain Cancer-A Review.

Due to their biocompatibility, non-toxicity, and surface-conjugation capabilities, liposomes are effective nanocarriers that can encapsulate chemotherapeutic drugs and facilitate targeted delivery across the blood-brain barrier (BBB). Additionally, strategies have been explored to synthesize liposomes that respond to internal and/or external stimuli to release their payload controllably. Although research into liposomes for brain cancer treatment is still in its infancy, these systems have great potential to fundamentally change the drug delivery landscape. This review paper attempts to consol

Совпадение в полном тексте источника
… Considered the most selective barrier in the human body, the BBB is primarily composed of tightly joined endothelial cells connected by tight junctions (TJs) and adherens junctions (AJs), along with a thin layer of pericytes. …

The Bone Marrow Microenvironment Mechanisms in Acute Myeloid Leukemia.

Bone marrow (BM) is a highly complex tissue that provides important regulatory signals to orchestrate hematopoiesis. Resident and transient cells occupy and interact with some well characterized niches to produce molecular and cellular mechanisms that interfere with differentiation, migration, survival, and proliferation in this microenvironment. The acute myeloid leukemia (AML), the most common and severe hematological neoplasm in adults, arises and develop in the BM. The osteoblastic, vascular, and reticular niches provide surface co-receptors, soluble factors, cytokines, and chemokines that

Extracellular RNA in melanoma: Advances, challenges, and opportunities.

Melanoma, a malignant mass lesion that originates in melanocytes and has a high rate of malignancy, metastasis, and mortality, is defined by these characteristics. Malignant melanoma is a kind of highly malignant tumor that produces melanin and has a high mortality rate. Its incidence accounts for 1%-3% of all malignant tumors and shows an obvious upward trend. The discovery of biomolecules for the diagnosis and treatment of malignant melanoma has important application value. So far, the exact molecular mechanism of melanoma development relevant signal pathway still remains unclear. According

Molecular Mechanisms of Bone Metastasis: Which Targets Came from the Bench to the Bedside?

Bone metastases ultimately result from a complex interaction between cancer cells and bone microenvironment. However, prior to the colonization of the bone, cancer cells must succeed through a series of steps that will allow them to detach from the primary tumor, enter into circulation, recognize and adhere to specific endothelium, and overcome dormancy. We now know that as important as the metastatic cascade, tumor cells prime the secondary organ microenvironment prior to their arrival, reflecting the existence of specific metastasis-initiating cells in the primary tumor and circulating osteo

Совпадение в полном тексте источника
… In another study, it was shown that breast cancer MICs located in the bone predominantly reside in a niche that exhibits features of osteogenesis, and that that niche interactions were mediated by heterotypic adherens junctions involving cancer-derived E-cadherin and osteogenic N-cadherin [ 49 ]. …

Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies.

Lysophosphatidic acid (LPA) is an abundant bioactive phospholipid, with multiple functions both in development and in pathological conditions. Here, we review the literature about the differential signaling of LPA through its specific receptors, which makes this lipid a versatile signaling molecule. This differential signaling is important for understanding how this molecule can have such diverse effects during central nervous system development and angiogenesis; and also, how it can act as a powerful mediator of pathological conditions, such as neuropathic pain, neurodegenerative diseases, an

Совпадение в полном тексте источника
… Cadherin-bound beta-catenin feeds into the Wnt pathway upon adherens junctions dissociation: Evidence for an intersection between beta-catenin pools. PLoS ONE. 2009;4:e4580. doi: 10.1371/journal.pone.0004580. 69. Murakami M, Shiraishi A, Tabata K, Fujita N. …

Peripheral Neuropathy under Oncologic Therapies: A Literature Review on Pathogenetic Mechanisms.

Peripheral neurologic complications are frequent adverse events during oncologic treatments and often lead to dose reduction, administration delays with time elongation of the therapeutic plan and, not least, worsening of patients' quality of life. Experience skills are required to recognize symptoms and clinical evidences and the collaboration between different health professionals, in particular oncologists and hospital pharmacists, grants a correct management of this undesirable occurrence. Some classes of drugs (platinates, vinca alkaloids, taxanes) typically develop this kind of side effe

UFMTrack, "Недоходный миграционный трекер", позволяющий проанализировать весь многоэтапный каскад экстравазии иммунных клеток через барьер кровеносного мозга в микрофлюидовых устройствах.

Эндотелиальный барьер кровеносного мозга (БДБ) строго контролирует оборот иммунных клеток в центральную нервную систему (КНС). В таких нейро-воспалительных заболеваниях, как множественный склероз, этот жесткий контроль, однако, нарушается, что приводит к инфильтрации иммунных клеток в CNS. Разработка моделей BBB in vitro в сочетании с микрофлюидовыми устройствами способствовала более глубокому пониманию клеточных и молекулярных механизмов посредничества многоэтапной экстравазии Т-клеток по всему BBB. Одним из основных узких мест в этих исследованиях in vitro является отсутствие надежного и авт

Совпадение в полном тексте источника
… The framework could be employed in combination of other methods, e.g., by incorporating fluorescently labeled endothelial adherens junctions one could differentiate the trans- from the paracellular transmigration in the migrating cells. …

High-Affinity DARPin Allows Targeting of MeV to Glioblastoma Multiforme in Combination with Protease Targeting without Loss of Potency.

Measles virus (MeV) is naturally cytolytic by extensive cell-to-cell fusion. Vaccine-derived MeV is toxic for cancer cells and is clinically tested as oncolytic virus. To combine the potential of MeV with enhanced safety, different targeting strategies have been described. We generated a receptor-targeted MeV by using receptor-blind viral attachment protein genetically fused to designed ankyrin repeat protein (DARPin) binding domains specific for the epidermal growth factor receptor (EGFR). To reduce on-target toxicity for EGFR+ healthy cells, we used an engineered viral fusion protein activat

Olive phenolics as c-Met inhibitors: (-)-Oleocanthal attenuates cell proliferation, invasiveness, and tumor growth in breast cancer models.

Dysregulation of the Hepatocyte growth factor (HGF)/c-Met signaling axis upregulates diverse tumor cell functions, including cell proliferation, survival, scattering and motility, epithelial-to-mesenchymal transition (EMT), angiogenesis, invasion, and metastasis. (-)-Oleocanthal is a naturally occurring secoiridoid from extra-virgin olive oil, which showed antiproliferative and antimigratory activity against different cancer cell lines. The aim of this study was to characterize the intracellular mechanisms involved in mediating the anticancer effects of (-)-oleocanthal treatment and the potent

Совпадение в полном тексте источника
… Previous studies showed that sustained activation of HGF/c-Met signaling is associated with dissociation of cadherin-based adherens junctions, followed by loss of E-cadherin expression [42] , [43] . …

Retinal Vein Occlusion-Background Knowledge and Foreground Knowledge Prospects-A Review.

Thrombosis of retinal veins is one of the most common retinal vascular diseases that may lead to vascular blindness. The latest epidemiological data leave no illusions that the burden on the healthcare system, as impacted by patients with this diagnosis, will increase worldwide. This obliges scientists to search for new therapeutic and diagnostic options. In the 21st century, there has been tremendous progress in retinal imaging techniques, which has facilitated a better understanding of the mechanisms related to the development of retinal vein occlusion (RVO) and its complications, and conseq

Совпадение в полном тексте источника
… The activation of the VEGF pathway, secondary to hypoxia, induces neovascularisation and increases vascular permeability in the retina by directly affecting tight junctions and adherens junctions of the endothelium [ 30 ]. …

Program-Abstracts

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Совпадение в полном тексте источника
… Junction Formation in Endothelial Cells 10:46 Pampee Young , Nashville, TN, USA Tumor-Derived, Low-Level TNFa Expression Augments the Formation of Tumor-Promoting Myeloid Subtype of Vascular Leukocytes Through the Upregulation of Integrin a 5 and Enhanced Binding to Fibronectin 10:58–11:30 Coffee … Interestingly, the activation of E-selectin induces a remodeling of EC that is associated with disruption of the adherens junctions. This leads to increased interendothelial spaces enabling transendothelial migration (Tremblay et al Oncogene 2006). …

Mechanisms of Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent side effects caused by antineoplastic agents, with a prevalence from 19% to over 85%. Clinically, CIPN is a mostly sensory neuropathy that may be accompanied by motor and autonomic changes of varying intensity and duration. Due to its high prevalence among cancer patients, CIPN constitutes a major problem for both cancer patients and survivors as well as for their health care providers, especially because, at the moment, there is no single effective method of preventing CIPN; moreover, the possibilities of treating t

Unraveling the Anticancer Effect of Curcumin and Resveratrol.

Resveratrol and curcumin are natural products with important therapeutic properties useful to treat several human diseases, including cancer. In the last years, the number of studies describing the effect of both polyphenols against cancer has increased; however, the mechanism of action in all of those cases is not completely comprehended. The unspecific effect and the ability to interfere in assays by both polyphenols make this challenge even more difficult. Herein, we analyzed the anticancer activity of resveratrol and curcumin reported in the literature in the last 11 years, in order to unr

Совпадение в полном тексте источника
… The same research group has demonstrated the anti-metastatic activity of curcumin in non-small cell lung cancer by decreasing the expression of early growth response protein 1 (EGR-1), and thereby reducing the adherens junctions and Wnt signaling pathway activity. …