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Emerging mechanism and therapeutic potential of neurofibromatosis type 1-related nerve system tumor: Advancing insights into tumor development.

Neurofibromatosis Type 1 (NF1) is a genetic disorder resulting from mutations in the NF1 gene, which increases susceptibility to various nervous system tumors, including plexiform neurofibromas, malignant peripheral nerve sheath tumors, and optic pathway gliomas. Recent research has shown that these tumors are intricately connected to the complex, dynamic interactions within neurons, culminating in neuronal signaling that fosters tumor growth. These interactions offer crucial insights into the molecular mechanisms underpinning tumor development, as well as broader implications for therapeutic

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… AMPA receptors, a type of ionotropic glutamate receptor, amplify glutamate-induced inward currents, increasing the excitability of malignant cells—a process potentially linked to the development of epilepsy in glioma patients. 123 Additionally, paracrine glutamate release through the cystine/glutamate …

The Impact of Iron on Cancer-Related Immune Functions in Oncology: Molecular Mechanisms and Clinical Evidence.

Iron metabolism plays a dual role in cancer, serving as an essential nutrient for cellular functions and a potential catalyst for tumor growth and immune evasion. Here, we cover the complex interplay between iron levels within the serum or in the microenvironment and cancer therapy, focusing on how iron deficiency and overload can impact immune function, tumor progression, and treatment efficacy. On the one hand, we highlight iron deficiency as a factor of primary immune responses and its adverse effects on anti-cancer immunotherapy efficacy. On the other hand, we also stress the impact of iro

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… The Cystine/Glutamate Antiporter System xc− in Health and Disease: From Molecular Mechanisms to Novel Therapeutic Opportunities. Antioxid. Redox Signal. 2013;18:522–555. doi: 10.1089/ars.2011.4391. 107. Buss J., Torti F., Torti S. The Role of Iron Chelation in Cancer Therapy. Curr. Med. …

Redox Remodeling by Nutraceuticals for Prevention and Treatment of Acute and Chronic Inflammation.

Antioxidant-rich dietary regimens are considered the best practice to maintain health, control inflammation, and prevent inflammatory diseases. Yet, nutraceuticals as food supplements are self-prescribed and purchasable over the counter by healthy individuals for the purpose of beneficial effects on fitness and aging. Hence, the effectiveness, safety, and correct intake of these compounds need to be better explored. Since redox-modulating activity of these compounds appears to be involved in activation and or suppression of immune cells, the preventive use of nutraceuticals is very attractive

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… Extracellular low redox potential (high GSH:GSSG ratio) and reducing conditions (APC-derived cystine, Cys2) are activation signals for naïve T cells that differentiate into T cells requiring anaerobic glycolysis, low level of intracellular ROS maintained by electron transport chain (ETC), and pentose …

Contribution of Macrophages and T Cells in Skeletal Metastasis.

Bone is a common site for metastases with a local microenvironment that is highly conducive for tumor establishment and growth. The bone marrow is replete with myeloid and lymphoid linage cells that provide a fertile niche for metastatic cancer cells promoting their survival and growth. Here, we discuss the role of macrophages and T cells in pro- and anti-tumoral mechanisms, their interaction to support cancer cell growth, and their contribution to the development of skeletal metastases. Importantly, immunotherapeutic strategies targeting macrophages and T cells in cancer are also discussed in

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… Similarly, T cells lack cystathionase to convert methionine into cysteine and the x c - transporter to import cystine, disulfide-bonded cysteine. They rely on DCs to directly supply the cysteine necessary for their activation and function [ 284 ]. …

Targetable pathways for drug repurposing in gastric cancer.

Gastric cancer (GC) is both the fifth most common cancer worldwide and the fifth in mortality. Owing to a lack of symptoms in the early stages and unspecific clinical presentation in the later stages, GC is usually diagnosed at advanced stages. This means that only approximately 60% of patients are eligible for curative treatment, and overall, GC patients have a 5-year survival rate of only 28.3%, underscoring the importance of developing new treatment strategies. Drug repurposing involves identifying new therapeutic uses for approved drugs and is a promising strategy for cancer treatment beca

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… Levobupivacaine upregulated the expression of miR-489-3p, which targets the cystine/glutamate transporter gene S LC7A11 and subsequently induces ferroptosis[ 107 ]. …

Frailty in Aging and the Search for the Optimal Biomarker: A Review.

In the context of accelerated aging of the population worldwide, frailty has emerged as one of the main risk factors that can lead to loss of self-sufficiency in older people. This syndrome is defined as a reduced state of physiological reserve and functional capacity. The main diagnostic tools for frailty are based on scales that show deficits compared to their clinical application, such as the Fried frailty phenotype, among others. In this context, it is important to have one or more biomarkers with clinical applicability that can objectively and precisely determine the degree or risk of fra

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… S-Methyl-L-Ergothioneine to L-Ergothioneine Ratio in Urine Is a Marker of Cystine Lithiasis in a Cystinuria Mouse Model Antioxidants 2021 10 1424 10.3390/antiox10091424 34573056 PMC8471778 135. Borodina I. Kenny L.C. McCarthy C.M. Paramasivan K. Pretorius E. Roberts T.J. van der Hoek S.A. …

Chronic Kidney Disease: Strategies to Retard Progression.

Chronic kidney disease (CKD), defined as the presence of irreversible structural or functional kidney damages, increases the risk of poor outcomes due to its association with multiple complications, including altered mineral metabolism, anemia, metabolic acidosis, and increased cardiovascular events. The mainstay of treatments for CKD lies in the prevention of the development and progression of CKD as well as its complications. Due to the heterogeneous origins and the uncertainty in the pathogenesis of CKD, efficacious therapies for CKD remain challenging. In this review, we focus on the follo

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… For example, cystine stones carry the highest risk of CKD progression, followed by uric acid and struvite stones [ 99 ]. Given the higher rate of recurrence, nephrolithiasis and urothithiasis in CKD should be well managed. Pathways leading to CKD may be stone-specific. …

Glutamine and cancer: metabolism, immune microenvironment, and therapeutic targets.

Glutamine is the most abundant amino acid in human serum, and it can provide carbon and nitrogen for biosynthesis, which is crucial for proliferating cells. Moreover, it is widely known that glutamine metabolism is reprogrammed in cancer cells. Many cancer cells undergo metabolic reprogramming targeting glutamine, increasing its uptake to meet their rapid proliferation demands. An increasing amount of study is being done on the particular glutamine metabolic pathways in cancer cells.Further investigation into the function of glutamine in immune cells is warranted given the critical role these

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… Cystine transporter SLC7A11/xCT in cancer: ferroptosis, nutrient dependency, and cancer therapy. Protein Cell. 2021;12(8):599–620. 10.1007/s13238-020-00789-5. 108. V. K et al., “glutamine addiction and therapeutic strategies in lung cancer,” Int J Mol Sci. 2019; 20(2). 10.3390/ijms20020252. 109. …

Parthenolide: pioneering new frontiers in hematological malignancies.

Hematological malignancies are the fifth most prevalent cancer category in developed countries, presenting significant treatment challenges. The side effects of chemotherapy and its non-selective nature have led researchers to explore combination therapies to enhance efficacy and improve patient outcomes. Parthenolide (PTL) emerges as a promising candidate, being the first small molecule identified for its selective action against leukemic stem cells. This article provides an overview of PTL's effects and its potential as a complementary treatment for hematological malignancies. A systematic s

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… Although the presence of mesenchymal stem cells (MSCs) diminished sensitivity to PTL, this effect was significantly restored with sulfasalazine (SSZ), a cystine uptake transporter inhibitor. …

Potential Approaches Versus Approved or Developing Chronic Myeloid Leukemia Therapy.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, continued use of these inhibitors has contributed to the increase in clinical resistance and the persistence of resistant leukemic stem cells (LSCs). So, there is an urgent need to introduce additional targeted and selective therapies to eradicate quiescent LSCs, and to avoid the relapse and disease progression. Here, we focused on emerging BCR-ABL targeted and non-BCR-ABL targeted drugs employed in clinical trials and on alternative CML treatments, including antioxidan

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… New Cyclic Cystine Bridged Peptides From the Sponge Suberites Waedoensis. Mar Drugs (2014) 12:2760–70. doi: 10.3390/md12052760 143. Lauritano C, Ianora A. Grand Challenges in Marine Biotechnology: Overview of Recent EU-Funded Projects. In: Grand Challenges in Biology and Biotechnology. …

Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.

Protein folding is a fundamental process ensuring that polypeptide chains acquire the correct three-dimensional structures required for biological function. This complex journey from nascent polypeptides to mature proteins is tightly regulated by the cellular proteostasis network-an integrated system of molecular chaperones, folding enzymes, and degradation machineries. Disruptions in this network lead to dysproteostasis, a pathological state implicated in a growing list of human diseases, including neurodegenerative disorders, metabolic syndromes, and cancer. In this review, we provide a comp

Molecular-Based Treatment Strategies for Osteoporosis: A Literature Review.

Osteoporosis is an unavoidable public health problem in an aging or aged society. Anti-resorptive agents (calcitonin, estrogen, and selective estrogen-receptor modulators, bisphosphonates, anti-receptor activator of nuclear factor κB ligand antibody along with calcium and vitamin D supplementations) and anabolic agents (parathyroid hormone and related peptide analogs, sclerostin inhibitors) have major roles in current treatment regimens and are used alone or in combination based on the pathological condition. Recent advancements in the molecular understanding of bone metabolism and in bioengin

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… Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am. J. Hum. …

[Immunotherapy - The New Era of Oncology].

In the field of immunotherapy, essential progress was achieved over the past years partially demonstrating long lasting therapeutic responses in different tumor entities. A better understanding of the interactions between the tumor and the immune system as well as the integration of immunotherapeutic approaches into clinical routine were the foundations for this development. The different approaches intervene on multiple levels of the immune response and directly or indirectly mount the patient's own immune defense against tumor cells. Immunotherapeutic approaches are represented by cytokine t

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… .2013.645 PMC3833228 42 Ostrand-Rosenberg S Sinha P Myeloid-derived suppressor cells: linking inflammation and cancer J Immunol 2009 182 4499 4506 19342621 10.4049/jimmunol.0802740 PMC2810498 43 Srivastava M K Sinha P Clements V K Myeloid-derived Suppressor Cells Inhibit T Cell Activation by Depleting Cystine …

A comprehensive review of Sjögren's syndrome: Classification criteria, risk factors, and signaling pathways.

Sjögren's syndrome (SS) is a chronic autoimmune disease that affects the exocrine glands and may lead to a range of systemic symptoms that impact various organs. Both innate and adaptive immune pathways might trigger the disease. Studying the signaling pathways underlying SS is crucial for enhancing diagnostic and therapeutic effectiveness. SS poses an ongoing challenge for medical professionals owing to the limited therapeutic options available. This review offers a comprehensive understanding of the intricate nature of SS, encompassing disease classification criteria, risk factors, and signa

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… IFN-γ triggers salivary gland epithelial cell ferroptosis by inhibiting cystine-glutamate exchange through the JAK-STAT1 pathway [ 164 ]. …

Myeloma bone disease: pathogenesis and management in the era of new anti-myeloma agents.

IntroductionMultiple myeloma (MM) is a malignancy of plasma cells with characteristic bone disease. Despite recent great strides achieved in MM treatment owing to the implementation of new anti-MM agents, MM is still incurable and bone destruction remains a serious unmet issue in patients with MM.ApproachIn this review, we will summarize and discuss the mechanisms of the formation of bone disease in MM and the available preclinical and clinical evidence on the treatment for MM bone disease.ConclusionsMM cells produce a variety of cytokines to stimulate receptor activator of nuclear factor-κB l

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… Sclerostin is a glycoprotein with a cystine knot-like domain that is almost exclusively expressed and produced by osteocytes [ 24 ]. Serum sclerostin levels are increased in patients with MM with bone lesions and correlate with clinical stages and the severity of bone destruction [ 13 ]. …

Advances in delivery methods of Arthrospira platensis (spirulina) for enhanced therapeutic outcomes.

Arthrospira platensis (A. platensis) aqueous extract has massive amounts of natural products that can be used as future drugs, such as C-phycocyanin, allophycocyanin, etc. This extract was chosen because of its high adaptability, which reflects its resolute genetic composition. The proactive roles of cyanobacteria, particularly in the medical field, have been discussed in this review, including the history, previous food and drug administration (FDA) reports, health benefits and the various dose-dependent therapeutic functions that A. platensis possesses, including its role in fighting against

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… This is a complete protein surplus that includes all important amino acids that the human body requires, including leucine, isoleucine, and valine, with small amounts of methionine, cystine, and lysine [ 32 , 33 ] in comparison with normal proteins such as beef, egg or milk. …

Curcumin Rewires the Tumor Metabolic Landscape: Mechanisms and Clinical Prospects.

Metabolic reprogramming is a fundamental hallmark and a key driver of malignant tumors. By reshaping glucose, lipid, and amino acid metabolism, as well as mitochondrial function, it sustains the abnormal proliferation and survival of tumor cells, making it a crucial target for anti-tumor therapy. Curcumin, a natural multi-target compound, exhibits unique advantages in intervening in tumor metabolic reprogramming due to its low toxicity and broad-spectrum regulatory properties. In various tumor models, it can directly modulate the activity of key glycolytic enzymes, such as hexokinase 2, lactat

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… ccRCC | 786-O-DR | Ferroptosis, Redox metabolism | reduce the intracellular iron concentration and reduce the expression of NCOA4, FTH1 and p53 by up regulating ADAMTS18 gene | [ 15 ] Curcumin analog, MitoCur-1 | Melanoma | A375, SKMEL28 | Ferroptosis, Redox metabolism | 1—inhibition of SLC7A11 blocks cystine … In melanoma cells, the analog MitoCur-1 inhibits cystine uptake by targeting SLC7A11 and suppresses the deubiquitinating enzyme USP14. …

Development of a machine learning-based predictive risk model combining fatty acid metabolism and ferroptosis for immunotherapy response and prognosis in prostate cancer.

Prostate cancer (PCa) remains a leading cause of cancer-related mortality, necessitating robust prognostic models and personalized therapeutic strategies. This study integrated bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics to construct a prognostic model based on genes shared between ferroptosis and fatty acid metabolism (FAM). Using the TCGA-PRAD dataset, we identified 73 differentially expressed genes (DEGs) at the intersection of ferroptosis and FAM, of which 19 were significantly associated with progression-free survival (PFS). A machine learning-

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… Moreover, therapeutic resistance, a major challenge in prostate cancer treatment, has been linked to ferroptosis evasion mechanisms such as the upregulation of GPX4 and the cystine/glutamate antiporter (system Xc −). …

Integrated Engineering of CAR-T Cells for Solid Tumours.

Chimeric antigen receptor (CAR) T-cell therapy has achieved durable efficacy in hematologic malignancies but encounters persistent obstacles in solid tumours, including antigen heterogeneity, a suppressive tumour microenvironment (TME), and intrinsic T-cell dysfunction. This review examines the transition from single-axis engineering to an integrated framework that addresses these hurdles in sequence. We delineate how next-generation CAR-T cells are designed for precise spatiotemporal activation through logic-gated and pharmacologically regulatable receptors, while being reinforced by metaboli

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… framework | Enhanced cytotoxicity against CD19‐CAR relapsed samples | Refractory B‐cell malignancies | [ 115 ] LILRB1 CAR‐T | Targeting immune checkpoint on B‐ALL/B‐NHL | Activity against CD19‐CAR resistant clones | Salvage therapy for CD19‐/CD20‐immunotherapy failures | [ 116 ] SLC3A2 CAR‐T | Targeting cystine … SLC3A2, a cystine transporter markedly overexpressed in multiple tumours, increased CAR‐T efficacy in xenograft models with low toxicity [ 117 ] (Figure 6F ). …

Monoclonal Gammopathies and the Bone Marrow Microenvironment: From Bench to Bedside and Then Back Again.

Multiple myeloma (MM) is an incurable hematologic malignancy characterized by a multistep evolutionary pathway, with an initial phase called monoclonal gammopathy of undetermined significance (MGUS), potentially evolving into the symptomatic disease, often preceded by an intermediate phase called "smoldering" MM (sMM). From a biological point of view, genomic alterations (translocations/deletions/mutations) are already present at the MGUS phase, thus rendering their role in disease evolution questionable. On the other hand, we currently know that changes in the bone marrow microenvironment (TM

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… Myeloid-Derived Suppressor Cells Inhibit T-Cell Activation by Depleting Cystine and Cysteine. Cancer Res. 2010;70:68–77. doi: 10.1158/0008-5472.CAN-09-2587. 30. Yu J., Du W., Yan F., Wang Y., Li H., Cao S., Yu W., Shen C., Liu J., Ren X. …