Результаты поиска

Bone Marrow Stromal Antigen 2 Is a Novel Plasma Biomarker and Prognosticator for Colorectal Carcinoma: A Secretome-Based Verification Study.

BackgroundThe cancer cell secretome has been recognized as a valuable reservoir for identifying novel serum/plasma biomarkers for different cancers, including colorectal cancer (CRC). This study aimed to verify four CRC cell-secreted proteins (tumor-associated calcium signal transducer 2/trophoblast cell surface antigen 2 (TACSTD2/TROP2), tetraspanin-6 (TSPAN6), bone marrow stromal antigen 2 (BST2), and tumor necrosis factor receptor superfamily member 16 (NGFR)) as potential plasma CRC biomarkers.MethodsThe study population comprises 152 CRC patients and 152 controls. Target protein levels in

Совпадение в полном тексте источника
… It was found to stabilize membrane microdomains, to participate in cell adhesion and cell migration, and to block virus budding [ 35 – 37 ]. 2.2. Patient Population and Clinical Specimens All clinical samples were collected at Chang Gung Memorial Hospital (Taoyuan, Taiwan). … CD317/tetherin is an organiser of membrane microdomains. Journal of Cell Science. 2013;126(7):1553–1564. doi: 10.1242/jcs.112953. 36. Evans D. T., Serra-Moreno R., Singh R. K., Guatelli J. C. BST-2/tetherin: a new component of the innate immune response to enveloped viruses. …

Calcium microdomains near R-type calcium channels control the induction of presynaptic long-term potentiation at parallel fiber to purkinje cell synapses.

R-type calcium channels in postsynaptic spines signal through functional calcium microdomains to regulate a calcium/calmodulin-sensitive potassium channel that in turn regulates postsynaptic hippocampal long-term potentiation (LTP). Here, we ask whether R-type calcium channels in presynaptic terminals also signal through calcium microdomains to control presynaptic LTP. We focus on presynaptic LTP at parallel fiber to Purkinje cell synapses in the cerebellum (PF-LTP), which is mediated by calcium/calmodulin-stimulated adenylyl cyclases. Although most presynaptic calcium influx is through N-type

Constitutively active protein kinase B enhances Lck and Erk activities and influences thymocyte selection and activation.

Protein kinase B (PKB), a serine threonine kinase is critically involved in cellular proliferation and survival. To characterize its role in T cell development in vivo, we have analyzed transgenic mice that express a membrane-targeted constitutively active version of PKB (myr PKB) in thymocytes and peripheral T cells. We report that myr PKB renders proliferative responses of thymocytes more sensitive to TCR signals by increased and sustained activation of Src kinase Lck and the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway. In addition, the proliferative respon

Carbohydrate Targets for CAR T Cells in Solid Childhood Cancers.

Application of the CAR targeting strategy in solid tumors is challenged by the need for adequate target antigens. As a consequence of their tissue origin, embryonal cancers can aberrantly express membrane-anchored gangliosides. These are carbohydrate molecules consisting of a glycosphingolipid linked to sialic acids residues. The best-known example is the abundant expression of ganglioside GD2 on the cell surface of neuroblastomas which derive from GD2-positive neuroectoderm. Gangliosides are involved in various cellular functions, including signal transduction, cell proliferation, differentia

Декодирование GPCR, сигнализирующее перепрограммирование рака: молекулярные механизмы и терапевтические последствия.

G белковые рецепторы (GPCR) представляют собой крупнейшую мембранную группу рецепторов в геноме человека и служат ключевыми регуляторами клеточного сигнала, гомеостаза и фармакологической реакции. Помимо их классической роли в посредничестве внеклеточной стимуляции по зависящим от G-протеина и независимым путям, которые играют ключевую роль при помощи GPCR сигнальных путей, включая CAMP-PKA/EPAC, IP3/PLC, PI3K/Akt/mTOR и ERK/MAPK cascades, в вождении онкогенного распространения, апоптоза и метастаза. Кроме того, ГПХР замешаны в опухоли с помощью различных молекулярных механизмов, в рамках кото

Some mechanisms of FLIP expression in inhibition of HIV-1 replication in Jurkat cells, CD4+ T cells and PBMCs.

HIV-1 infection and replication are affected by host factors. Recent studies demonstrate that molecules from apoptotic pathways regulate HIV-1 replication. Therefore, studies on effects of host factors that maintain host cell survival and influence HIV-1 replication are critical to understanding the mechanisms of HIV-1 replicative cycle. Using the susceptible Jurkat cell line, CD4(+) T cells, and peripheral blood mononuclear cells (PBMCs), we studied the role of FLIP, an inhibitor of caspase-8, in HIV-1 production. Full length cellular FLIP (cFLIP) inhibited HIV-1 replication in these cells. c

The novel Akt inhibitor, perifosine, induces caspase-dependent apoptosis and downregulates P-glycoprotein expression in multidrug-resistant human T-acute leukemia cells by a JNK-dependent mechanism.

A significant impediment to the success of cancer chemotherapy is the occurrence of multidrug resistance, which, in many cases, is attributable to overexpression of membrane transport proteins, such as the 170-kDa P-glycoprotein (P-gp). Also, upregulation of the phosphatidylinositol 3-kinase (PI3K)/Akt-signaling pathway is known to play an important role in drug resistance, and has been implicated in the aggressiveness of a number of different cancers, including T-acute lymphoblastic leukemia (T-ALL). We have investigated the therapeutic potential of the novel Akt inhibitor, perifosine (a synt

Docosahexaenoic Acid Modulates a HER2-Associated Lipogenic Phenotype, Induces Apoptosis, and Increases Trastuzumab Action in HER2-Overexpressing Breast Carcinoma Cells.

In breast cancer, lipid metabolic alterations have been recognized as potential oncogenic stimuli that may promote malignancy. To investigate whether the oncogenic nature of lipogenesis closely depends on the overexpression of HER2 protooncogene, the normal breast cell line, HB4a, was transfected with HER2 cDNA to obtain HER2-overexpressing HB4aC5.2 cells. Both cell lines were treated with trastuzumab and docosahexaenoic acid. HER2 overexpression was accompanied by an increase in the expression of lipogenic genes involved in uptake (CD36), transport (FABP4), and storage (DGAT) of exogenous fat

Совпадение в полном тексте источника
… Its final product, palmitate, is frequently used to synthesize membrane microdomains [ 1 , 15 , 19 ]. In a previous study, when this pathway was inhibited by omega-3 docosahexaenoic fatty acid (DHA), lipid rafts were disrupted and cell apoptosis was induced [ 15 ]. … Chemical-physical changes in cell membrane microdomains of breast cancer cells after omega-3 PUFA incorporation Cell Biochemistry and Biophysics 2012 64 1 45 59 10.1007/s12013-012-9365-y 2-s2.0-84865556815 22622660 50 Abel S. Riedel S. Gelderblom W. C. A. …

The Glycocalyx and Its Role in Vascular Physiology and Vascular Related Diseases.

PurposeIn 2007 the two senior authors wrote a review on the structure and function of the endothelial glycocalyx layer (Weinbaum in Annu Rev Biomed Eng 9:121-167, 2007). Since then there has been an explosion of interest in this hydrated gel-like structure that coats the luminal surface of endothelial cells that line our vasculature due to its important functions in (A) basic vascular physiology and (B) vascular related diseases. This review will highlight the major advances that have occurred since our 2007 paper.MethodsA literature search mainly focusing on the role of the glycocalyx in the

Sphingolipid metabolism and hematologic disorders: current understanding and future directions.

Sphingolipids are not only key structural components of cell membranes but also serve as important signaling molecules, and their metabolic homeostasis is essential for the maintenance of cellular functions. In recent years, with the advancement of technologies such as metabolomics, studies have revealed that sphingolipid metabolic abnormalities are extensively involved in the occurrence and development of various hematological disorders, including immune thrombocytopenia, myeloproliferative neoplasms, graft-versus-host disease, hereditary hematological diseases, and hematologic malignancies.

Совпадение в полном тексте источника
… For instance, ceramides with different N-acyl chain lengths exhibit distinct phase behavior, interfacial elasticity, and lateral mixing within membranes, thereby modulating the structure and function of membrane microdomains ( Fanani and Maggio, 2017 ). … Dynamic studies have shown that the aggregation state of sphingolipids within membrane microdomains (e. g., lipid rafts) changes in response to external stimuli. …

Omega-3 Fatty Acids and Cancer Cell Cytotoxicity: Implications for Multi-Targeted Cancer Therapy.

Cancer is a major disease worldwide. Despite progress in cancer therapy, conventional cytotoxic therapies lead to unsatisfactory long-term survival, mainly related to development of drug resistance by tumor cells and toxicity towards normal cells. n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can exert anti-neoplastic activity by inducing apoptotic cell death in human cancer cells either alone or in combination with conventional therapies. Indeed, n-3 PUFAs potentially increase the sensitivity of tumor cells to conventional therapies, poss

Cbl-b is a negative regulator of receptor clustering and raft aggregation in T cells.

Stimulation of T cells via the antigen and costimulatory receptors leads to the organization of a supramolecular activation cluster called the immune synapse. We report that loss of the molecular adaptor Cbl-b in T cells frees antigen receptor-triggered receptor clustering, lipid raft aggregation, and sustained tyrosine phosphorylation from the requirement for CD28 costimulation. Introduction of the cbl-b mutation into a vav1-/- background relieved the functional defects of vav1-/- T cells and caused spontaneous autoimmunity. Wiscott Aldrich Syndrome protein (WASP) was found to be essential fo

Библиометрический и биоинформатический анализ перерождения в многократной миеломе: тенденции и горячих точек исследований и связанные с ними генетические пути (Associated Geneal Pathways)2000-2023).

ЦЕЛЬ: Цель настоящего исследования заключается в проведении библиометрического визуального анализа и биоинформатического анализа для изучения исследовательских горячих точек и тенденций развития почечных расстройств в множестве миелом, включая соответствующие гены и каналы сигнала в прошлом. two десятилетиями. МЕТОДЫ: База данных " Web of Science Core Collection " использовалась в качестве источника данных для извлечения литературы о дефектах почек в множестве миеломы. 2000 в адрес 2023. Выбранная литература была проанализирована с использованием библиометрического и биоинформатическ

Effect of PLA2G6 and SMPD1 Variants on the Lipid Metabolism in the Cerebrospinal Fluid of Patients with Parkinson's Disease: A Non-targeted Lipidomics Study.

IntroductionSleep patterns are more frequently interrupted in patients with Parkinson's disease (PD), and it is still unclear whether genetic factors are involved in PD-related sleep disorders. In this study, we hypothesize that PD-associated genetic risk affects lipid metabolism, which in turn contributes to different types of sleep disorders.MethodsWe used a non-targeted lipidomics to explore the lipid composition of cerebrospinal fluid (CSF) exosomes derived from patients with PD carrying phospholipase A2 Group VI (PLA2G6) and sphingomyelin phosphodiesterase 1 (SMPD1) mutations.ResultsPLA2G

Совпадение в полном тексте источника
… Cholesterol and sphingomyelin (SM) in exosomes also form ordered lipid raft membrane microdomains, fine-tuning membrane fluidity, and altering protein localization. …

Assessment of TSPAN Expression Profile and Their Role in the VSCC Prognosis.

The role and prognostic value of tetraspanins (TSPANs) in vulvar squamous cell carcinoma (VSCC) remain poorly understood. We sought to primarily determine, at both the molecular and tissue level, the expression profile of the TSPANs CD9, CD63, CD81, and CD82 in archived VSCC samples (n = 117) and further investigate their clinical relevance as prognostic markers. Our studies led us to identify CD63 as the most highly expressed TSPAN, at the gene and protein levels. Multicomparison studies also revealed that the expression of CD9 was associated with tumor size, whereas CD63 upregulation was ass

The Role of Drug Repurposing in the Development of Novel Antimicrobial Drugs: Non-Antibiotic Pharmacological Agents as Quorum Sensing-Inhibitors.

Background: The emergence of multidrug-resistant organisms (MDROs) is a global public health issue, severely hindering clinicians in administering appropriate antimicrobial therapy. Drug repurposing is a drug development strategy, during which new pharmacological applications are identified for already approved drugs. From the viewpoint of the development of virulence inhibitors, inhibition of quorum sensing (QS) is a promising route because various important features in bacterial physiology and virulence are mediated by QS-dependent gene expression. Methods: Forty-five pharmacological agents,

Совпадение в полном тексте источника
… Atorvastatin was effective in a 1–2-fold lower dose than simvastatin; although the exact mechanism of action is uncertain, some reports suggest that they interfere with the mevalonate pathway (similarly to eukaryotic cells) and the synthesis of the major lipid constituents of cell membrane microdomains … Recent Advances in Anti-virulence Therapeutic Strategies With a Focus on Dismantling Bacterial Membrane Microdomains, Toxin Neutralization, Quorum-Sensing Interference and Biofilm Inhibition Front. Cell Infect. Microbiol. 2019 9 74 10.3389/fcimb.2019.00074 31001485 PMC6454102 52. Bhardwaj A.K. …

Lomitapide repurposing for treatment of malignancies: A promising direction.

The development of novel drugs from basic science to clinical practice requires several years, much effort, and cost. Drug repurposing can promote the utilization of clinical drugs in cancer therapy. Recent studies have shown the potential effects of lomitapide on treating malignancies, which is currently used for the treatment of familial hypercholesterolemia. We systematically review possible functions and mechanisms of lomitapide as an anti-tumor compound, regarding the aspects of apoptosis, autophagy, and metabolism of tumor cells, to support repurposing lomitapide for the clinical treatme

Modulating glycosphingolipid metabolism and autophagy improves outcomes in pre-clinical models of myeloma bone disease.

Patients with multiple myeloma, an incurable malignancy of plasma cells, frequently develop osteolytic bone lesions that severely impact quality of life and clinical outcomes. Eliglustat, a U.S. Food and Drug Administration-approved glucosylceramide synthase inhibitor, reduced osteoclast-driven bone loss in preclinical in vivo models of myeloma. In combination with zoledronic acid, a bisphosphonate that treats myeloma bone disease, eliglustat provided further protection from bone loss. Autophagic degradation of TRAF3, a key step for osteoclast differentiation, was inhibited by eliglustat as ev

Трекеты (Trk-Targeting Drugs): Новинная терапия различных заболеваний.

Многие маршруты могут привести к переходу от здорового к больному фенотипу. Однако не так уж много путей, чтобы двигаться в противоположном направлении, т.е. Таким образом, остается следующий насущный вопрос: каковы патогенные пути и как можно противодействовать им в терапевтических целях? Человеческие клетки содержат >500 белковые киназы и почти 200 белковые фосфаты, действующие на тысячи белков, включая факторы роста клеток. Здесь мы обсуждаем нейтрофины с патогенными или метаботрофными способностями, в частности нейротрофический фактор, полученный из мозга, фактор нервного роста (НГФ), про-

Action of Phytochemicals on Insulin Signaling Pathways Accelerating Glucose Transporter (GLUT4) Protein Translocation.

Diabetes is associated with obesity, generally accompanied by a chronic state of oxidative stress and redox imbalances which are implicated in the progression of micro- and macro-complications like heart disease, stroke, dementia, cancer, kidney failure and blindness. All these complications rise primarily due to consistent high blood glucose levels. Insulin and glucagon help to maintain the homeostasis of glucose and lipids through signaling cascades. Pancreatic hormones stimulate translocation of the glucose transporter isoform 4 (GLUT4) from an intracellular location to the cell surface and