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Circadian clocks and adaptive immune function: from mechanisms to therapeutic applications.

The circadian clock exerts profound regulatory control over adaptive immunity, particularly affecting T and B lymphocyte development, trafficking, activation, and effector function. These immune cells possess autonomous molecular clocks governed by core genes such as Bmal1, Clock, Per1/2, and Cry1/2, which influence transcriptional programs related to receptor expression, cytokine signaling, and metabolism. Circadian regulation shapes the daily oscillation of lymphocyte recirculation through lymphoid organs, modulates antigen responsiveness, and fine-tunes subset differentiation-most notably s

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… In contrast, lymphocyte egress is regulated by the Sphingosine-1-Phosphate Receptor 1 (S1PR1), which promotes the release of lymphocytes into efferent lymphatic vessels ( 31 ). …

Глубинные пространственные омики MLADI-MS, управляемые квантовой каскадной лазерной микроскопией среднего инфракрасного изображения.

В пространственной "omics " высокоуверенные молекулярные идентификации необходимы для исследования сложной биологии и для пространственной биомаркировки. Однако нынешняя масс-спектрометрическая съемка (MSI) на основе пространственной "омики" должна скомпрометировать скорость получения данных и глубину биохимического профилирования. Здесь мы введём быструю, без этикеток квантовую каскадную лазерную микроскопию среднего инфракрасного изображения (QCL-MIR), чтобы направить MSI в высокоинтересные области тканей, такие маленькие, как гломерули почки, культурные многоклеточные сфероидные я

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… The example of fingolimod (FTY720), an S1PR antagonist that blocks the inflammatory actions of the related signaling lipid sphingosine-1-phosphate (S1P) suggests that analogous CerP signaling blockers may be attainable 67 . …

Mutual connected IL-6, EGFR and LIN28/Let7-related mechanisms modulate PD-L1 and IGF upregulation in HNSCC using immunotherapy

The development of techniques and immunotherapies are widely applied in cancer treatment such as checkpoint inhibitors, adoptive cell therapy, and cancer vaccines apart from radiation therapy, surgery, and chemotherapy give enduring anti-tumor effects. Minority people utilize single-agent immunotherapy, and most people adopt multiple-agent immunotherapy. The difficulties are resolved by including the biomarkers to choose the non-responders’ and responders’ potentials. The possibility of the potential complications and side effects are examined to improve cancer therapy effects. The Head and Ne

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… GPCRs, like the sphingosine 1 phosphate receptor 1/2 (S1PR1/2) and angiotensin II (Ang II), and some TLRs, like TLR 2, 3, 4, 7, and 9, can also mediate STAT3 activation ( 39 ). STAT3 mutations are rare only in patients with hematological malignancies ( 17 ). …

Circular RNAs and Drug Resistance in Genitourinary Cancers: A Literature Review.

In recent years, systematic treatment has made great progress in genitourinary tumors. However, some patients develop resistance to the treatments, resulting in an increase in mortality. Circular RNAs (circRNAs) form a class of non-coding RNAs with high stability and significant clinical relevance. Accumulating evidence indicates that circRNAs play a vital role in cancer development and tumor chemotherapy resistance. This review summarizes the molecular and cellular mechanisms of drug resistance mediated by circRNAs to common drugs used in the treatment of genitourinary tumors. Several circRNA

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… In addition, miRNA-451a is downregulated by circ-FNTA, and the effect of miRNA-451a is to reduce the level of Sphingosine-1-phosphate Receptor 3 (S1PR3). The increase of circ-FNTA promotes the progression and chemo-resistance of BCa [ 81 ]. …

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

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… Other mechanisms of neurotoxicity have been proposed to clarify bortezomib-induced PN, one of which regards its ability to increase sphingolipid metabolism within astrocytes with a subsequent increasing levels of ceramide, sphingosine-1 phosphate (S1P) and dihydrosphingosine-1-phosphate (DH-S1P), that …

The biogenesis and biological function of PIWI-interacting RNA in cancer.

Small non-coding RNAs (ncRNAs) are vital regulators of biological activities, and aberrant levels of small ncRNAs are commonly found in precancerous lesions and cancer. PIWI-interacting RNAs (piRNAs) are a novel type of small ncRNA initially discovered in germ cells that have a specific length (24-31 nucleotides), bind to PIWI proteins, and show 2'-O-methyl modification at the 3'-end. Numerous studies have revealed that piRNAs can play important roles in tumorigenesis via multiple biological regulatory mechanisms, including silencing transcriptional and posttranscriptional gene processes and a

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… Hence, the expression of piR-004800 has been found to be regulated by the sphingosine-1-phosphate receptor and thus activates or inhibits the PI3K/AKT/mTOR signaling pathway [ 79 ]. …

MicroRNA Express Profiles как биомаркеры реакции на корректирующую болезнь терапию при множественном склерозе: системный обзор.

Хотя микроРНК (миРНК) являются активной областью исследований в области множественного склероза (МС) и были предложены в качестве потенциальных биомаркеров реакции на лечение, имеющиеся данные по-прежнему трудно интерпретировать. В рамках этого систематического обзора изучается взаимосвязь между выражением miRNA и реакцией на корректирующие заболевания методы лечения (DMT) у взрослых с MS. С момента создания базы данных PubMed/MedLINE и веб-страницы научных исследований проводились систематические обыски 11 Февраль 2026. Fifteen исследования, которые сравнивали выражение miRNA между респондент

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… The search strategy combined controlled vocabulary (medical subject headings [MeSH]) and free-text terms related to MS, miRNAs, and DMTs (interferon-beta [IFN-β], glatiramer acetate [GA], dimethyl fumarate [DMF], teriflunomide, fingolimod (formerly FTY720), siponimod, ozanimod, ponesimod, sphingosine …

Exercise-mobilized donor lymphocyte infusions enhanced with cytokine stimulation for the prevention and treatment of leukemic relapse after allogeneic hematopoietic cell transplantation.

Donor lymphocyte infusions (DLI) are a standard therapy following allogeneic hematopoietic cell transplantation (alloHCT) for preventing and treating leukemic relapse in high-risk patients, particularly those with myeloid malignancies such as acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS). However, the efficacy of DLI remains suboptimal and is accompanied by a significant risk of life-threatening graft-versus-host disease (GvHD), highlighting the urgent need for strategies that enhance graft-versus-leukemia (GvL) effects while mitigating GvHD.

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… The sphingosine-1-phosphate (S1P) and S1P-receptor (S1PR) gradient pathway, which regulates immune cell egress from blood and secondary lymphoid organs to sites of injury, was found to play a significant role in this mobilization. …

Chemistry and Pharmacology of Fluorinated Drugs Approved by the FDA (2016-2022).

Fluorine is characterized by high electronegativity and small atomic size, which provide this molecule with the unique property of augmenting the potency, selectivity, metabolic stability, and pharmacokinetics of drugs. Fluorine (F) substitution has been extensively explored in drug research as a means of improving biological activity and enhancing chemical or metabolic stability. Selective F substitution onto a therapeutic or diagnostic drug candidate can enhance several pharmacokinetic and physicochemical properties such as metabolic stability and membrane permeation. The increased binding a

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… Relugolix | | Nonpeptide GnRH receptor antagonist | [ 106 ] Ripretinib | | Protein kinase inhibitor | [ 107 ] Rucaparib | | Polymerase inhibitor | [ 108 ] Selinexor | | Selective nuclear transport (SINE) inhibitor | [ 109 ] Selumetinib | | Selective MEK 1 and MEK 2 inhibitor | [ 110 ] Siponimod | | Sphingosine …

Primed for global coronavirus pandemic: Emerging research and clinical outcome.

The global effort to combat and contain the coronavirus disease 2019 (COVID-19) caused by the recently discovered severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now proceeding on a war footing. The world was slow to react to the developing crisis, but once the contours of the impending calamity became evident, the different state and non-state actors have raced to put their act together. The COVID-19 pandemic has blatantly exposed the shortcomings of our healthcare system and the limitations of medical science, despite considerable advances in recent years. To effectively tack

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… University,China | Phase 2 Clinical Study in China NCT04273581 , NCT04273529 ( ClinicalTrials.gov ) | Mechanism of action is not fully understood 11 | Fingolimod (14) | First Affiliated Hospital of Fujian Medical University,China | Phase-II Clinical Study in China NCT04280588 ( ClinicalTrials.gov ) | Sphingosine …

Reversing Autoimmunity Combination of Rituximab and Intravenous Immunoglobulin.

In this concept paper, the authors present a unique and novel protocol to treat autoimmune diseases that may have the potential to reverse autoimmunity. It uses a combination of B cell depletion therapy (BDT), specifically rituximab (RTX) and intravenous immunoglobulin (IVIg), based on a specifically designed protocol (Ahmed Protocol). Twelve infusions of RTX are given in 6-14 months. Once the CD20+ B cells are depleted from the peripheral blood, IVIg is given monthly until B cells repopulation occurs. Six additional cycles are given to end the protocol. During the stages of B cell depletion,

Neuropathic cancer pain: What we are dealing with? How to manage it?

Cancer pain is a serious health problem, and imposes a great burden on the lives of patients and their families. Pain can be associated with delay in treatment, denial of treatment, or failure of treatment. If the pain is not treated properly it may impair the quality of life. Neuropathic cancer pain (NCP) is one of the most complex phenomena among cancer pain syndromes. NCP may result from direct damage to nerves due to acute diagnostic/therapeutic interventions. Chronic NCP is the result of treatment complications or malignancy itself. Although the reason for pain is different in NCP and non

Hypoxia within the glioblastoma tumor microenvironment: a master saboteur of novel treatments.

Glioblastoma (GBM) tumors are the most aggressive primary brain tumors in adults that, despite maximum treatment, carry a dismal prognosis. GBM tumors exhibit tissue hypoxia, which promotes tumor aggressiveness and maintenance of glioma stem cells and creates an overall immunosuppressive landscape. This article reviews how hypoxic conditions overlap with inflammatory responses, favoring the proliferation of immunosuppressive cells and inhibiting cytotoxic T cell development. Immunotherapies, including vaccines, immune checkpoint inhibitors, and CAR-T cell therapy, represent promising avenues f

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… Interestingly, a variety of brain tumors induce reduced expression of cell membrane sphingosine-1-phosphate receptor (S1P1), which causes trapping of T cells in bone marrow, and therefore actively induces an immunosuppressive state ( 22 ). …

Gut-Bone Axis: A Non-Negligible Contributor to Periodontitis.

Periodontitis is a polymicrobial infectious disease characterized by alveolar bone loss. Systemic diseases or local infections, such as diabetes, postmenopausal osteoporosis, obesity, and inflammatory bowel disease, promote the development and progression of periodontitis. Accumulating evidences have revealed the pivotal effects of gut microbiota on bone health via gut-alveolar-bone axis. Gut pathogens or metabolites may translocate to distant alveolar bone via circulation and regulate bone homeostasis. In addition, gut pathogens can induce aberrant gut immune responses and subsequent homing o

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… Sphingosine-1-phosphate (S1P) is the major regulator of lymphocyte migration out of lymph nodes. Depending on gradient concentration of S1P, effector T cells expressing S1P receptor-1 (S1PR1) emigrate from lymph node to circulation ( Benechet et al., 2016 ; Yu et al., 2021 ). …

NK Cell-Based Immunotherapy in Renal Cell Carcinoma.

Natural killer (NK) cells are cytotoxic lymphocytes that are able to kill tumor cells without prior sensitization. It has been shown that NK cells play a pivotal role in a variety of cancers, highlighting their relevance in tumor immunosurveillance. NK cell infiltration has been reported in renal cell carcinoma (RCC), the most frequent kidney cancer in adults, and their presence has been associated with patients' survival. However, the role of NK cells in this disease is not yet fully understood. In this review, we summarize the biology of NK cells and the mechanisms through which they are abl

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… S1P5: Sphingosine-1-Phosphate receptor 5. LFA-1: Lymphocyte function-associated antigen 1. 3. Cell Surface Receptors and Cytotoxic Mechanisms NK cells induce cell death primarily through two different mechanisms. …

Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential.

Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow. In the vast majority of patients, this results in osteolytic

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… Pederson L Ruan M Westendorf JJ Khosla S Oursler MJ Regulation of bone formation by osteoclasts involves Wnt/BMP signaling and the chemokine sphingosine-1-phosphate Proc Natl Acad Sci U S A 2008 105 52 20764 20769 19075223 10.1073/pnas.0805133106 PMC2603259 54. …

Цереброспинный грипп и биомаркеры крови для нейроаксональных повреждений при многоразовом склерозе

После появления новых данных о том, что нейродегенеративные процессы в множестве склероза (MS) присутствуют на ранних стадиях, был проявлен активный научный интерес к биомаркерам нейро-аксональных повреждений в жидкостях организма пациентов, страдающих с склерозом. Недавно проведенные исследования позволили ввести новые потенциальные биомаркеры, но в то же время прояснили патогенетическое и клиническое значение хорошо известных. В настоящем документе рассматриваются имеющиеся данные о биомаркерах нейроаксональных повреждений в крови и цереброспинных жидкостях и освещается их связь с клинически

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… Sphingosine and FTY720 directly bind pro-survival 14-3-3 proteins to regulate their function. Cellular Signalling. 2010;22(9):1291–1299. doi: 10.1016/j.cellsig.2010.04.004. 185. Deisenhammer F, Egg R, Giovannoni G, et al. EFNS guidelines on disease-specific CSF investigations. …

Characteristics and advances in signaling pathways, cellular communication, cell junctions, and oxidative stress in lymphedema.

Lymphedema is a chronic inflammatory disease without an effective treatment method, and it results in a high disease burden and psychological distress in patients. Although there have been significant advances in targeted therapies, there are still no effective options to treat this refractory disease. In recent years, new advances and breakthroughs have been made in signaling pathways, including RAS/MAPK, PI3K/AKT, VEGF-C/VEGFR-3, HGF/MET, and TGF-β1, which are important for understanding the pathogenesis and disease progression of lymphedema. Mutations in genes encoding cell junctions affect

Phytochemical-Based Nanomedicine for Advanced Cancer Theranostics: Perspectives on Clinical Trials to Clinical Use.

In the current chapter, a new strategic compilation of phytochemicals with potent antitumor properties has been addressed, most importantly focusing on cell cycle arrest and apoptotic signaling mechanism. A promising approach in tumor prevention is to eliminate cancer cells preferably via cell cycle arrest and programmed cell death with lesser harm to neighboring normal cells. Cancer cells have a survival advantage to escape apoptosis and relentlessly divide to proliferate, gearing up the cell cycle process. Recently, the use of phytochemical-derived conjugated chemotherapeutic agents has incr

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… Additionally, liposomal curcumin has sphingosine kinase inhibitor activity, that warrants the use of liposomal curcumin monotherapy or in combination can reduce the recurrence of cancer and suitable for further clinical trials. 77 Altogether, these reports suggest that lipocurcumin is a safe drug and …

Small molecule metabolites: discovery of biomarkers and therapeutic targets.

Metabolic abnormalities lead to the dysfunction of metabolic pathways and metabolite accumulation or deficiency which is well-recognized hallmarks of diseases. Metabolite signatures that have close proximity to subject's phenotypic informative dimension, are useful for predicting diagnosis and prognosis of diseases as well as monitoring treatments. The lack of early biomarkers could lead to poor diagnosis and serious outcomes. Therefore, noninvasive diagnosis and monitoring methods with high specificity and selectivity are desperately needed. Small molecule metabolites-based metabolomics has b

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… Bladder Cancer Juntao Zhuang et al. 618 18 Serum Treatment NMR, UPLC-MS Glutamine, glutamate, hypoxanthine Amino acid pathways Colorectal cancer Yu Yuan et al. 676 30 Serum Function UPLC-MS Glycodeoxycholic acid Poly (ADP-ribose) polymerase-1 Breast cancer Yi Xiao et al. 22 330 Tissues Function LC-MS Sphingosine … | 18 | Serum | Treatment | NMR, UPLC-MS | Glutamine, glutamate, hypoxanthine | Amino acid pathways Colorectal cancer | Yu Yuan et al. 676 | 30 | Serum | Function | UPLC-MS | Glycodeoxycholic acid | Poly (ADP-ribose) polymerase-1 Breast cancer | Yi Xiao et al. 22 | 330 | Tissues | Function | LC-MS | Sphingosine …