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Hypophosphatemic rickets: diagnosis and treatment.

Hypophosphatemicrickets (HR) represents a heterogeneous group of disorders characterized by renal phosphate wasting, impaired bone mineralization, and skeletal deformities. This narrative review provides an overview of phosphate homeostasis and the molecular mechanisms underlying HR, focusing on the role of Fibroblast Growth Factor 23 (FGF23) in regulating renal phosphate use and vitamin D metabolism. The clinical, biochemical, and genetic features of both FGF23-dependent and -independent forms of HR are discussed, including X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic

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… Cystinosis is another major genetic cause, an autosomal recessive lysosomal storage disorder caused by pathogenic variants in the CTNS gene, which encodes the lysosomal cystine transporter ( 87 ) . … Cystine accumulation within lysosomes lead to tubular damage and dysfunction, manifesting as Fanconi syndrome in infancy. Without treatment, cystinosis progresses to end-stage renal disease (ESRD) ( 88 ) . …

Engagement of Mesenchymal Stromal Cells in the Remodeling of the Bone Marrow Microenvironment in Hematological Cancers.

Mesenchymal stromal cells (MSCs) are a subset of heterogeneous, non-hematopoietic fibroblast-like cells which play important roles in tissue repair, inflammation, and immune modulation. MSCs residing in the bone marrow microenvironment (BMME) functionally interact with hematopoietic stem progenitor cells regulating hematopoiesis. However, MSCs have also emerged in recent years as key regulators of the tumor microenvironment. Indeed, they are now considered active players in the pathophysiology of hematologic malignancies rather than passive bystanders in the hematopoietic microenvironment. Onc

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… Moreover, MSCs uptake cystine by overexpressing the cystine transporter [ 152 ]. Upon conversion to cysteine, it is released into microenvironment and internalized by leukemic cells for glutathione synthesis and the maintenance of the redox balance ( Figure 2 d) [ 152 ]. 2.5. … Stromal control of cystine metabolism promotes cancer cell survival in chronic lymphocytic leukaemia. Nat. Cell Biol. 2012;14:276–286. doi: 10.1038/ncb2432. 153. Korde N., Kristinsson S.Y., Landgren O. …

Mechanisms of ferroptotic and non-ferroptotic organ toxicity of chemotherapy: protective and therapeutic effects of ginger, 6-gingerol and zingerone in preclinical studies.

Chemotherapy (CT) is one of the flagship options for the treatment of cancers worldwide. It involves the use of cytotoxic anticancer agents to kill or inhibit the proliferation of cancer cells. However, despite its clinical efficacy, CT triggers side effect toxicities in several organs, which may impact cancer patient's quality of life and treatment outcomes. While the side effect toxicity is consistent with non-ferroptotic mechanisms involving oxidative stress, inflammation, mitochondrial impairment and other aberrant signalling leading to apoptosis and necroptosis, recent studies show that f

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… The process of its de novo synthesis occurs through the glutamate-cysteine transporter system called system Xc − , and the channel SLC7A11 which allows glutamate exit from the cell, and entry of cystine into the cell. … Subsequently, cystine is converted to cysteine, which is further utilized in the synthesis of GSH. CT drugs have the potential to inhibit the function of system Xc − , which may lead to a reduction in GSH levels and activity of glutathione peroxidase-4 (GPX-4). …

NF-κB in Cell Deaths, Therapeutic Resistance and Nanotherapy of Tumors: Recent Advances.

The transcription factor nuclear factor-κB (NF-κB) plays a complicated role in multiple tumors. Mounting evidence demonstrates that NF-κB activation supports tumorigenesis and development by enhancing cell proliferation, invasion, and metastasis, preventing cell death, facilitating angiogenesis, regulating tumor immune microenvironment and metabolism, and inducing therapeutic resistance. Notably, NF-κB functions as a double-edged sword exerting positive or negative influences on cancers. In this review, we summarize and discuss recent research on the regulation of NF-κB in cancer cell deaths,

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… Cystine/glutamate antiporter system xc−, whose primary component is SLC7A11, functions as a cystine/glutamate antiporter to formulate GSH. GSH is converted into GSSG under the catalysis of GPX4, neutralizing the oxidative substances in the plasma membrane, and thus inhibiting ferroptosis. …

Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.

Reactive oxygen species (ROS) act as critical secondary messengers in various intracellular signaling pathways that regulate cellular proliferation, differentiation, and survival under normal physiological conditions. However, dysregulation of redox signaling-driven by genetic mutations, epigenetic alterations, and posttranscriptional or posttranslational modifications-plays a central role in malignant transformation and cancer progression. Cancer cells typically exhibit elevated basal ROS levels due to increased metabolic activity, mitochondrial dysfunction, and oncogene activation. This mode

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… In disulfidptosis, glucose starvation in SLC7A11-overexpressing cells causes ROS-mediated NADPH depletion, impairing cysteine-to-cystine conversion, resulting in abnormal disulfide bond formation in cytoskeletal proteins and structural collapse. … In disulfidptosis, glucose starvation in SLC7A11-overexpressing cells causes ROS-mediated NADPH depletion, impairing cysteine-to-cystine conversion, resulting in abnormal disulfide bond formation in cytoskeletal proteins and structural collapse. …

Management of urinary stones by experts in stone disease (ESD 2025).

The formation of kidney stones is a complex biologic process involving interactions among genetic, anatomic, dietary, and environmental fact … olic and dermatologic side effects. Urease inhibitors for struvite stones and drugs used to enhance cystine solubility are more frequently associated with side effects. The use of smartphone applications can support patients by promoting adequate hydration, adherence to dietary recommendations, and compliance with prophylactic medication. Endoscopic techn …

Crystalline deposits in the cornea and various areas of the kidney as symptoms of an underlying monoclonal gammopathy: a case report.

BACKGROUND: Plasma cell dyscrasias (PCD) are characterized by an abnormal production of intact monoclonal immunoglobulins or parts such as heavy or light chains. In most cases, the monoclonal protein (also termed paraprotein) is produced by a clonal plasma cell population. The production of monoclonal proteins can result in deposits of various types and localization depending on the type, amount, and electrochemical properties of the paraprotein. One histopathologic presentation, albeit rare, are crystalline deposits. They can form in various organs and hence cause a wide spectrum of symptoms.

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… Cystinosis, which often presents with corneal deposits, could be ruled out via measurement of cystine content of peripheral blood leukocytes, which was only slightly elevated at 0,3 μmol/g protein (< 0,2 μmol/g protein). A molecular analysis showed no mutation in the CTNS-gene. …

Noncanonical SQSTM1/p62-Nrf2 pathway activation mediates proteasome inhibitor resistance in multiple myeloma cells via redox, metabolic and translational reprogramming.

Multiple Myeloma (MM) is a B-cell malignancy characterized by the accumulation of clonal plasma cells in the bone marrow, with drug resistance being a major cause of therapeutic failure. We established a carfilzomib-resistant derivative of the LP-1 MM cell line (LP-1/Cfz) and found that the transcription factor NF-E2 p45-related factor 2 (Nrf2; gene symbol NFE2L2) contributes to carfilzomib resistance. The mechanism of Nrf2 activation involved enhanced translation of Nrf2 as well as its positive regulator, the autophagy receptor sequestosome 1 (SQSTM1)/p62. The eukaryotic translation initiatio

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… To determine whether antioxidant defense conferred protection to carfilzomib in these MM models and whether there was a contribution of FAO, the cells were cotreated with carfilzomib and either (S)-4-carboxyphenylglycine, an inhibitor of xCT (a subunit of the x c − cystine antiporter involved in glutathione … Treatment with (S)-4-carboxyphenylglycine (CPG), an inhibitor of xCT (a subunit of the x c − cystine antiporter involved in glutathione homeostasis encoded by the SLC7A11 gene) sensitizes LP-1/Cfz cells (left graph) and KMS-11/Cfz cells (right graph) to carfilzomib. …

Oxidative Stress: Signaling Pathways, Biological Functions, and Disease.

The dysregulated accumulation of reactive oxygen species (ROS) and reactive nitrogen species disrupts redox homeostasis, triggering oxidative stress (OS) and driving pathophysiological changes across multiple organ systems. OS modulates critical signaling pathways, induces inflammation, impairs mitochondrial function, alters metabolic homeostasis, and dysregulates autophagy, contributing to disease progression. While prior research has largely focused on OS within single-organ diseases (e.g., neurodegenerative, cardiovascular, and oncological disorders), the systemic role of OS in pan-organ di

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… Key tumor suppressors, such as p53 and BAP1, promote ferroptosis by repressing the expression of antioxidant defense components like SLC7A11, a subunit of the cystine/glutamate antiporter system Xc− responsible for cystine uptake required for GSH synthesis, and GPX4 [ 307 , 308 , 309 ]. …

Selenium Compounds as Novel Potential Anticancer Agents.

The high number of new cancer incidences and the associated mortality continue to be alarming, leading to the search for new therapies that would be more effective and less burdensome for patients. As there is evidence that Se compounds can have chemopreventive activity, studies have begun to establish whether these compounds can also affect already existing cancers. This review aims to discuss the different classes of Se-containing compounds, both organic and inorganic, natural and synthetic, and the mechanisms and molecular targets of their anticancer activity. The chemical classes discussed

Network Pharmacology Identifies Therapeutic Targets and the Mechanisms of Glutathione Action in Ferroptosis Occurring in Oral Cancer.

Oral cancer (OC) is one of the most pernicious cancers with increasing incidence and mortality worldwide. Surgery is the primary approach for the treatment of early-stage OC, which reduces the quality of life of the patients. Therefore, there is an urgent need to discover novel treatments for OC. Targeting ferroptosis to induce cell death through the modulation of lipid oxidation has been used as a new approach to treat many cancers. Glutathione (GSH) is a coenzyme factor of GSH peroxidase 4, and it carries potential applicability in treating OC. By using network pharmacology and molecular doc

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… Oncogene-Selective Sensitivity to Synchronous Cell Death Following Modulation of the Amino Acid Nutrient Cystine. Cell Rep 18 (11), 2547–2556. PMID: 28297659; PMCID: PMC5368412. 10.1016/j.celrep.2017.02.054 Pramanik K. K., Mishra R. (2022). …

The Potential and Prospects of Marine Drugs in Intervening Nerve-Tumor Crosstalk.

The bidirectional crosstalk between the nervous system and tumors has emerged as a transformative new frontier in both precision oncotherapy and mechanism-driven cancer pain management. Marine natural products with inherent neuroactive properties exhibit unparalleled intervention advantages for targeting this complex pathophysiological axis. Herein, we systematically and prospectively dissect the multi-layered bidirectional communication between the nervous system and malignancies, comprehensively summarize the pivotal contributions of marine-derived bioactive molecules to advances in neurosci

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… Sea Anemone Peptide Ms11a-3 Ms11a-3 is a 42-membered peptide isolated from the sea anemone Metridium senile with an inhibitor cystine knot fold structure. … Peptides from the Sea Anemone Metridium senile with Modified Inhibitor Cystine Knot (ICK) Fold Inhibit Nicotinic Acetylcholine Receptors. Toxins. 2022;15:28. doi: 10.3390/toxins15010028. 62. Araoz R., Servent D., Molgó J., Iorga B.I., Fruchart-Gaillard C., Benoit E., Gu Z., Stivala C., Zakarian A. …

A malignant symbiosis: The neuro-metabolic symphony rewires the tumor microenvironment.

Emerging evidence in cancer neuroscience has established a reciprocal bidirectional loop between neural signaling and tumor metabolism as a central driver of malignant progression. This review critically evaluates bidirectional neuro-metabolic symbiosis and its profound implications for overcoming treatment refractoriness. We first analyzed the anterograde mechanism, in which peripheral nerve terminals and systemic endocrine factors impose distinct metabolic dependencies on malignant and stromal cell populations. By forcing alterations in nutrient utilization pathways, these neural cues create

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… Knocking out the cystine/glutamate antiporter xCT solute carrier family 7 member 11 (SLC7A11) has been proven to significantly impairs the metastatic routes of breast cancer without compromising the host's systemic immune function [ 68 ]. … Cystine/glutamate antiporter xCT deficiency reduces metastasis without impairing immune system function in breast cancer mouse models. J. Exp. Clin. Cancer Res. 2023;42(1):254. doi: 10.1186/s13046-023-02830-x. 69. Specht C., Tapia A., Penrod S., Soriano G.A., Awawdeh A., Alshawi S.A., et al. …

Role of TRP Channels in Cancer-Induced Bone Pain.

The burden of cancer is growing in almost every country. Bone metastases significantly affect the prognosis and lead to an increase in mortality and morbidity. The management of cancer-induced bone pain (CIBP) still shows various unmet needs. Opioid use is burdened by a number of possible side effects. Moreover, recent progresses in cancer treatment significantly increased the life expectancy of cancer patients, even those with metastatic disease. In this narrative review, we reported the main findings regarding TRP channel function in cancer pain models. TRP cation channels play a key role in

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… CPZ can modulate the cystine/glutamate antiporter, which was linked to CIBP induction via excessive glutamate secretion from distal breast cancer metastases. … The cystine/glutamate antiporter system xc- drives breast tumor cell glutamate release and cancer-induced bone pain. Pain. 2016;157:2605–2616. doi: 10.1097/j.pain.0000000000000681. 60. Liu D., Zhou X., Tan Y., Yu H., Cao Y., Tian L., Yang L., Wang S., Liu S., Chen J., et al. …

Chronic Psychological Stress in Oncogenesis: Multisystem Crosstalk and Multimodal Interventions.

Malignant tumors constitute a major global public health burden. Chronic psychological stress (CPS) manifests as sustained dysregulation arising from prolonged adaptive responses to chronic endogenous and exogenous stimuli. Clinical evidence indicates that CPS markedly influences cancer progression, with most oncology patients developing detectable stress-related psychological disorders during disease management. This review synthesizes recent advances in understanding CPS-mediated oncogenic mechanisms and evaluates current intervention approaches. Mechanistically, CPS compromises immune surve

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… Amino acid metabolic dysregulation critically contributes to stress-associated tumor progression, and CPS coactivates the amino acid transporter SLC7A11/xCT in tumor cells [ 102 ] and promotes cystine uptake and glutathione biosynthesis, protecting against both oxidative stress and ferroptosis [ 103 … SLC7A11 → ↑cystine uptake → ↑glutathione → protection against oxidative stress and ferroptosis [ 102 ] Lymphoma | DA/NK/cAMP | DA → DRD2/DRD3/DRD4 (D2-like receptors) on NK cells → ↑Gi protein → ↓adenylate cyclase → ↓cAMP → ↓PKA → ↓p-CREB → ↓cytotoxicity [ 56 ] Interventions for CPS in Cancer Patients …

Guided immunotherapy for residual solid tumor: integrating platelets and CAR T cells to reduce post-surgical recurrence.

Postoperative recurrence remains a major obstacle to durable remission in patients with solid tumors, even after complete macroscopic resection. Growing evidence suggests that surgery creates a transient yet highly permissive biological window characterized by inflammatory signaling, coagulation activation, endothelial disruption, and systemic immune suppression. Together, these processes foster a protective niche that enables microscopic residual disease to evade immune surveillance and initiate metastatic outgrowth. Although modern adjuvant therapies have improved outcomes, their effectivene

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… /ferroptosis susceptibility SLC7A11/xCT → glutathione/ferroptosis Erastin-like agents, SLC7A11 inhibitors Small molecules Preclinical Blocks cystine import, depletes glutathione, promotes ferroptosis and immune sensitization [ 157 – 159 ] Glucose metabolism Glycolysis blockade Hexokinase/glycolytic flux … /ferroptosis susceptibility | SLC7A11/xCT → glutathione/ferroptosis | Erastin-like agents, SLC7A11 inhibitors | Small molecules | Preclinical | Blocks cystine import, depletes glutathione, promotes ferroptosis and immune sensitization | [ 157 – 159 ] Glucose metabolism | Glycolysis blockade | Hexokinase …

Plasma микроRNA Подпись как предсказательный знак клинической реакции на терапию во время множественного склероза.

ЦЕЛЬ: Несмотря на наличие эффективных методов лечения множественного склероза (MS), непредсказуемый характер развития заболеваний и изменчивость результатов индивидуального лечения требуют надежных биомаркеров. Цель этого экспериментального исследования заключается в изучении потенциала плазмы, циркулирующей микроРНК (миРНК), в качестве биомаркеров-метилфумаратов для клинической реакции на диметил-фумарат (ДМП), широко применяемой пероральной обработки НР. МЕТОДЫ: Образцы периферальной крови были взяты из nineteen лиц с повторными выбросами MS (PwRRMS) до и после 3, 6, 12, и 24 месяцев управле

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… A recent study indicates that DMF‐induced NRF2 activation stimulates the cystine/glutamate antiporter solute carrier (SLC)7A11, enhancing GSH production, ROS removal, and regulatory T cell expansion, which promotes immune tolerance [ 13 ]. …

Metabolomic Profiling in the Characterization of Degenerative Bone and Joint Diseases.

Osteoarthritis and inflammatory arthropathies are a cause of significant morbidity globally. New research elucidating the metabolic derangements associated with a variety of bone and joint disorders implicates various local and systemic metabolites, which further elucidate the underlying molecular mechanisms associated with these destructive disease processes. In osteoarthritis, atty acid metabolism has been implicated in disease development, both locally and systemically. Several series of rheumatoid arthritis patients have demonstrated overlapping trends related to histidine and glyceric aci

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… Hydroxyproline was elevated in the group of patients with a lower bone mineral density, which corresponded with preclinical work by Ma et al., while glycylglycine and cystine were significantly decreased [ 45 , 46 ]. …

Metabolic reprogramming and cisplatin resistance: the emerging role of Pyruvate Dehydrogenase Kinases (PDKs).

Cisplatin resistance remains a primary obstacle in oncology, leading to therapeutic failure and disease recurrence. While resistance mechanisms are multifactorial, metabolic reprogramming has emerged as a critical adaptive strategy for cancer cells to evade cisplatin-induced cytotoxicity. This review synthesizes current evidence on how altered metabolism drives cisplatin resistance, with a particular emphasis on the pivotal role of pyruvate dehydrogenase kinases (PDKs). PDKs act as metabolic gatekeepers by inhibiting the pyruvate dehydrogenase complex (PDHC), diverting glucose flux away from m

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… Sulfasalazine (SASP), an FDA-approved anti-inflammatory drug, inhibits the xCT (cystine transporter) transporter and has antiproliferative effects on NSCLC [ 112 ]. Taken together, these findings suggest that targeting amino acid metabolism represents a promising therapeutic avenue. …

Доклиническая оценка клеток DC-CCK как потенциально эффективной иммунотерапии для лечения глиобластомы.

Несмотря на благоприятное воздействие иммунотерапии на различные виды раковых заболеваний, ее полный успех в борьбе с вредителями CNS по-прежнему сопряжен с трудностями. Недавно в результате успешного клинического испытания клеточной иммунотерапии, вызванной цитокинами, у пациентов с глиобластомой (ГБМ) открылась новая возможность для иммунотерапии с использованием клеточной селекции в малиньях CNS. На основе этих выводов мы изучили вопрос о том, могут ли дендритные клетки (DC) в сочетании с цитокиновыми клетками-убийцами (DC-CCK) также обеспечить альтернативный и более эффективный способ повы

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… Overexpression of cystine/glutamate antiporter xCT correlates with nutrient flexibility and ZEB1 expression in highly clonogenic glioblastoma stem-like cells (GSCs). Cancers (Basel) 13 , (2021). 10.3390/cancers13236001 PMC8672273 34885110 …