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The BE (2)-M17 neuroblastoma cell line: revealing its potential as a cellular model for Parkinson's disease.

Parkinson's disease is a pathology with a wide range of in vivo and in vitro models available. Among these, the SH-SY5Y neuroblastoma cell line is one of the most employed. This model expresses catecholaminergic markers and can differentiate and acquire various neuronal phenotypes. However, challenges persist, primarily concerning the variability of growth media, expression of dopaminergic markers, and a wide variety of differentiation protocols have been reported in the literature without direct comparison between them. This lack of standardized differentiation conditions impacts result repro

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… Small molecule of sphingosine as a rescue of dopaminergic cells: A cell therapy approach in neurodegenerative diseases therapeutics. J. Cell. Physiol. 234 11401–11410. 10.1002/jcp.27774 Taylor T. N., Caudle W. M., Miller G. W. (2011). …

Analysis of microRNA expression profiles in exosomes derived from acute myeloid leukemia by p62 knockdown and effect on angiogenesis.

ObjectivesIn this study, we aimed to investigate the effect of p62 on angiogenesis and microRNA (miRNA) expression profiles in acute myeloid leukemia (AML) exosomes.MethodsAn Exiqon v19.0 microRNA MicroArray was used to profile miRNAs in exosomes derived from parental and p62-knockdown U937 cells. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to predict the biological functions and potential mechanisms of differentially expressed miRNAs in AML exosomes. Endothelial cell tube formation assays using human umbilical vein endothelial cells (HUVECs) w

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… McLachlan T Alvaro F Enjeti AK Verrills NM Dun MD 2018 Targeting oncogenic signaling in mutant FLT3 acute myeloid leukemia: the path to least resistance International Journal of Molecular Sciences 19 10 3198 10.3390/ijms19103198 PMC6214138 30332834 Sun et al. (2010) Sun HY Wei SP Xu RC Xu PX Zhang WC 2010 Sphingosine …

The Endosteal Niche in Breast Cancer Bone Metastasis.

The establishment of bone metastasis remains one of the most frequent complications of patients suffering from advanced breast cancer. Patients with bone metastases experience high morbidity and mortality caused by excessive, tumor-induced and osteoclast-mediated bone resorption. Anti-resorptive treatments, such as bisphosphonates, are available to ease skeletal related events including pain, increased fracture risk, and hypercalcemia. However, the disease remains incurable and 5-year survival rates for these patients are below 25%. Within the bone, disseminated breast cancer cells localize in

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… In turn, osteoclasts secrete factors such as Wnt 10b, sphingosine-1-phosphate and bone morphogenic protein 6 (BMP-6) to regulate osteoblast differentiation and function. …

Protein kinase CK2: a potential therapeutic target for diverse human diseases.

CK2 is a constitutively active Ser/Thr protein kinase, which phosphorylates hundreds of substrates, controls several signaling pathways, and is implicated in a plethora of human diseases. Its best documented role is in cancer, where it regulates practically all malignant hallmarks. Other well-known functions of CK2 are in human infections; in particular, several viruses exploit host cell CK2 for their life cycle. Very recently, also SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has been found to enhance CK2 activity and to induce the phosphorylation of several CK2 substrates (ei

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… The identified mechanism relies on the regulation of the expression in glomeruli of diabetic renal fibrotic factors, such as fibronectin and intercellular adhesion molecule-1, under the control of CK2 through NFκB. 260 Furthermore, the overexpression of sphingosine kinase 1 was suggested as the mediator …

The role of hypoxic microenvironment in autoimmune diseases.

The hypoxic microenvironment, characterized by significantly reduced oxygen levels within tissues, has emerged as a critical factor in the pathogenesis and progression of various autoimmune diseases (AIDs). Central to this process is the hypoxia-inducible factor-1 (HIF-1), which orchestrates a wide array of cellular responses under low oxygen conditions. This review delves into the multifaceted roles of the hypoxic microenvironment in modulating immune cell function, particularly highlighting its impact on immune activation, metabolic reprogramming, and angiogenesis. Specific focus is given to

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… HIF-1 also modulates the expression of pro-angiogenic chemokines and their receptors, notably: stromal cell-derived factor-1α (SDF-1α) and sphingosine-1-phosphate (S1P), along with their cognate receptors such as CXCR4. …

Multiple myeloma cancer stem cells.

Multiple myeloma (MM) remains incurable despite much progress that has been made in the treatment of the disease. MM cancer stem cell (MMSC), a rare subpopulation of MM cells with the capacity for self-renewal and drug resistance, is considered to lead to disease relapse. Several markers such as side population (SP) and ALDH1+ have been used to identify MMSCs. However, ideally and more precisely, the identification of the MMSCs should rely on MMSCs phenotype. Unfortunately the MMSC phenotype has not been properly defined yet. Drug resistance is the most important property of MMSCs and contribu

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… D Mo Y Li MT Zou SW Cheng ZL Sun YP Xiong Y Guan KL Lei QY NOTCH-induced aldehyde dehydrogenase 1A1 deacetylation promotes breast cancer stem cells The Journal of clinical investigation 2014 124 5453 5465 25384215 10.1172/JCI76611 PMC4348941 65 Hirata N Yamada S Shoda T Kurihara M Sekino Y Kanda Y Sphingosine …

2022 NATIONAL CONGRESS OF THE ITALIAN SOCIETY OF HYPERTENSION (SIIA)

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Конвергенция глобальных эпидемий: диабет как модулятор нейродегенеративных и нейро-воспалительных расстройств.

Диабет меллитус (ДМ) и неврологические расстройства быстро совпадают с глобальным бременем на здоровье, обусловленным старением населения, растущей распространенностью метаболического синдрома, а также ограниченностью возможностей раннего обнаружения и коррекции заболеваний для многих неврологических синдромов. Помимо своей устоявшейся роли в периферической нейропатии, связанной с диабетом, DM все чаще используется в качестве изменяющего фактора риска, фенотипа и прогнозирования широкого спектра заболеваний центральной и периферической нервной системы. В ходе этого обзора мы обобщаем текущие э

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… By contrast, in the pre-clinical setting, sphingosine-1-phosphate (S1P) receptor modulators approved for MS (e.g., fingolimod, ozanimod, and Siponimod) have demonstrated potential metabolic benefits relevant for diabetes. …

Unveiling the global research status and intellectual map of cancer and immunosuppressants.

BackgroundThe use of immune checkpoint inhibitors (ICIs) has significantly advanced cancer therapy, improving survival rates and prognosis for many patients. This study employs bibliometric methods to explore the current state and future trends in the field of immunosuppressants and cancer treatment.MethodsData were retrieved from the Science Citation Index Expanded for articles and reviews published between 2014 and 2024 in the Web of Science database. 2,352 records were analyzed using CiteSpace, VOSviewer, R software, and Microsoft Excel. The focus was on publication trends, citations, co-ci

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… Cluster 5 (Dark Blue) primarily includes activation, NF-kappa B, and sphingosine 1 phosphate, which are closely related to the mechanisms of action of immunosuppressive agents. Cluster 6 (Purple) primarily includes immune-related adverse events, skin cancer, ICIs, and lung cancer. …

Последние достижения в области мезенхимической стволовой клеточной терапии для множественных склерозов: клинические виды применения и проблемы.

Множественный склероз (MS), хроническое аутоиммунное расстройство центральной нервной системы (CNS), характеризуется воспалением, обезвоживанием и нейродегенерацией, что приводит к различным клиническим проявлениям, таким, как усталость, сенсорное расстройство и когнитивная дисфункция. Текущее фармакологическое лечение направлено прежде всего на иммунную модуляцию, но не позволяет остановить прогрессию заболеваний или полностью обратить на нет повреждения CNS. Лечение стволовыми клетками (MSC) является многообещающей альтернативой, используя иммуномудуляторы, нейрозащиту и регенеративные спосо

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… Wang et al. also demonstrated that transplanting sphingosine kinase 1 (SPK1) gene-modified UC-MSCs (UCMSC-SPK1) significantly decreased the intensity of the neurological impairment in EAE mice models by reducing axonal loss, demyelination, and astrogliosis. …

TGF-β: an active participant in the immune and metabolic microenvironment of multiple myeloma : TGF-β in the microenvironment of multiple myeloma.

Although substantial quantities of potent therapies for multiple myeloma (MM) have been established, MM remains an incurable disease. In recent years, our understanding of the initiation, development, and metastasis of cancers has made a qualitative leap. Cancers attain the abilities to maintain proliferation signals, escape growth inhibitors, resist cell death, induce angiogenesis, and more importantly, escape anti-tumor immunity and reprogram metabolism, which are the hallmarks of cancers. Besides, different cancers have different tumor microenvironments (TME), thus, we pay more attention to

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… It also prevents memory T cells from leaving secondary lymphoid organs by downregulating KLF2, causing the decrease of sphingosine-1-phosphate receptor 1 (S1P1) expression and ultimately establishing T-cell retention in tissues [ 54 ]. …

The Health-Promoting Effects and the Mechanism of Intermittent Fasting.

Intermittent fasting (IF) is an eating pattern in which individuals go extended periods with little or no energy intake after consuming regular food in intervening periods. IF has several health-promoting effects. It can effectively reduce weight, fasting insulin levels, and blood glucose levels. It can also increase the antitumor activity of medicines and cause improvement in the case of neurological diseases, such as memory deficit, to achieve enhanced metabolic function and prolonged longevity. Additionally, IF activates several biological pathways to induce autophagy, encourages cell renew

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… cAMP-response element-binding protein; IGF-1: insulin-like growth factor-1; AMPK: AMP-dependent protein kinase; PS-1: presenilin-1; PSD95: postsynaptic density-95; TrkB: tropomyosin receptor kinase B; Atg13: autophagy-associated gene 13; BNIP3: Bcl2/adenovirus E1B 19 kD-interacting protein 3; SPK2: sphingosine …

Применение мезенхимальных ячеек и их эксзоом в нейродегенеративных заболеваниях и лизосомных заболеваниях.

Мезенхимальные стромальные клетки (МСЦ) стали перспективной терапевтической платформой для расстройств центральной нервной системы, включая нейродегенеративные заболевания и лизосомные расстройства хранения (ЛСД). В настоящем обзоре рассматриваются механизмы КБМ, связанные с активностью паракрина, иммуномодуляцией, воздействием антиоксидантов, регулированием с помощью ТФЭБ, а также с ферментатической перекрестной корректировкой в ЛСД, хотя и критически оцениваются проблемы перевода. Мы проводим сравнительный анализ источников КБМ, административных маршрутов, дозирующих режимов и характеристик

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… In mouse models of NPD, transplantation of BM-MSCs has been shown to prevent Purkinje cell death in the cerebellum and reduce levels of the toxic sphingosine. These findings indicate that MSCs can directly modulate metabolic pathways disrupted in LSDs [ 86 ]. …

Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications.

Cellular signaling pathways involved in the maintenance of the equilibrium between cell proliferation and apoptosis have emerged as rational targets that can be exploited in the prevention and treatment of cancer. Epigallocatechin-3-gallate (EGCG) is the most abundant phenolic compound found in green tea. It has been shown to regulate multiple crucial cellular signaling pathways, including those mediated by EGFR, JAK-STAT, MAPKs, NF-κB, PI3K-AKT-mTOR, and others. Deregulation of the abovementioned pathways is involved in the pathophysiology of cancer. It has been demonstrated that EGCG may exe

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… Sphingosine kinase-1 inhibitor (safingol) significantly sensitizes multiple myeloma cells to EGCG and could help in reducing the dose of the phytochemical [ 211 ]. …

Fertility Preservation in Female Patients with Cancer. Part I: Challenges and Future Prospects in Developing Countries; A Narrative Review Study.

While international guidelines on oncofertility practice have been published in developed countries, there is limited information available on oncofertility practice in developing countries, which often face limitations in their cancer health support networks. As survival rates improve in the field of cancer and other diseases, there is a growing need for stronger oncofertility services in developing countries. Given that 50% of cancer patients are under the age of 65, many of these patients are of reproductive age and preserving their fertility health prior to starting treatment is valuable.

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… Several drugs, including sphingosine-1-phosphate (S1P), AS101, and imatinib, have been designed to reduce chemotherapeutic-induced apoptosis in these cells ( 22 ). Radiotherapy Important factors related to fertility in radiotherapy are the dose and site of irradiation. …

The Role of Gamma Delta T Lymphocytes in Physiological and Pathological Condition-Focus on Psoriasis, Atopic Dermatitis, Autoimmune Disorders, Cancer and Lymphomas.

Gamma delta (γδ) T cells are a heterogeneous population of cells that play roles in inflammation, host tissue repair, clearance of viral and bacterial pathogens, regulation of immune processes, and tumor surveillance. Recent research suggests that these are the main skin cells that produce interleukin-17 (I-17). Furthermore, γδ T cells exhibit memory-cell-like characteristics that mediate repeated episodes of psoriatic inflammation. γδ T cells are found in epithelial tissues, where many cancers develop. There, they participate in antitumor immunity as cytotoxic cells or as immune coordinators.

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… CD69 is supposed to act as a signal that prevents TRM from leaving tissues by blocking the sphingosine-1-phosphate receptor 1 (S1PR1) [ 36 ]. CD8(+) CD69(+) CD103(+) TRM cells are a well-characterized subtype that develops in the epidermis. …

The Dual Role of Autophagy in Crizotinib-Treated ALK+ ALCL: From the Lymphoma Cells Drug Resistance to Their Demise.

Autophagy has been described as harboring a dual role in cancer development and therapy. Depending on the context, it can exert either pro-survival or pro-death functions. Here, we review what is known about autophagy in crizotinib-treated ALK+ ALCL. We first present our main findings on the role and regulation of autophagy in these cells. Then, we provide literature-driven hypotheses that could explain mechanistically the pro-survival properties of autophagy in crizotinib-treated bulk and stem-like ALK+ ALCL cells. Finally, we discuss how the potentiation of autophagy, which occurs with combi

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… As an example, Young et al. demonstrated in MEFs treated with sphingosine kinase inhibitor (SKI) that ATG5- and ATG16L-positive autophagosomal membranes were required to form an efficient intracellular death-inducing signaling complex (iDISC) containing Fas-associated protein with death domain (FADD) …

Novel drug targets for personalized precision medicine in relapsed/refractory diffuse large B-cell lymphoma: a comprehensive review.

Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous lymphoid malignancy and the most common subtype of non-Hodgkin's lymphoma in adults, with one of the highest mortality rates in most developed areas of the world. More than half of DLBLC patients can be cured with standard R-CHOP regimens, however approximately 30 to 40 % of patients will develop relapsed/refractory disease that remains a major cause of morbidity and mortality due to the limited therapeutic options.Recent advances in gene expression profiling have led to the identification of at least three distinct molecular

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… GCB-DLBCL is also associated with loss of sphingosine-1-phosphate receptor-2 (S1PR2) - G-protein alpha 13 (Gα13) signaling, which negatively modulates GC B-cell migration and PI3K signaling [ 15 – 17 , 84 ]. … Abbreviations: S1PR2 sphingosine-1-phosphate receptor-2, Gα13 (GNA13) heterotrimeric G protein alpha 13, ARHGEF1 Rho guanine nucleotide exchange factor (GEF) 1, PI3K phosphoinositide 3-kinase, mTORC1 mammalian target of rapamycin (mTOR) complex 1, BCL6 B cell lymphoma protein 6, BCL2 B cell lymphoma …

A Drug Screening Reveals Minocycline Hydrochloride as a Therapeutic Option to Prevent Breast Cancer Cells Extravasation across the Blood-Brain Barrier.

Among breast cancer (BC) patients, 15-25% develop BC brain metastases (BCBM), a severe condition due to the limited therapeutic options, which points to the need for preventive strategies. We aimed to find a drug able to boost blood-brain barrier (BBB) properties and prevent BC cells (BCCs) extravasation, among PI3K, HSP90, and EGFR inhibitors and approved drugs. We used BCCs (4T1) and BBB endothelial cells (b.End5) to identify molecules with toxicity to 4T1 cells and safe for b.End5 cells. Moreover, we used those cells in mixed cultures to perform a high-throughput microscopy screening of dru

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… Fingolimod (or FTY720) is an immunomodulator, specifically a sphingosine-1-phosphate receptor modulator, approved as therapy for patients with relapsing forms of multiple sclerosis [ 20 ]. …

Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics.

Treatment of blood malignancies and other cancer diseases has been mostly unfeasible, so far. Therefore, novel treatment regimens should be developed and the currently used ones should be further elaborated. A stable component in various cancer treatment regimens consists of vincristine, an antimitotic compound of natural origin. Despite its strong anticancer activity, mostly, it cannot be administered as monotherapy due to its unspecific action and severe side effects. However, vincristine is suitable for combination therapy. Multidrug treatment regimens including vincristine are standardly a

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… The development and maintenance of paclitaxel-induced neuropathic pain require activation of the sphingosine 1-phosphate receptor subtype 1 J. Biol. Chem. 2014 289 21082 21097 10.1074/jbc.M114.569574 24876379 PMC4110312 19. Starobova H. Monteleone M. Adolphe C. Batoon L. Sandrock C.J. Tay B. …