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Post-transplant cyclophosphamide-induced cardiotoxicity: A comprehensive review.

Cyclophosphamide-induced cardiotoxicity, associated with its toxic metabolite acrolein, is a significant concern and unresolved issue, especially when cyclophosphamide is administrated in high doses. However, cardiotoxicity following low-dose cyclophosphamide has been also documented, especially in post-hematopoietic stem cell transplantation (post-HSCT) settings. Despite the involvement of multiple signaling pathways in cyclophosphamide-induced cardiomyopathy, the exact underlying mechanisms remain to be fully elucidated. This review outlines the current challenges of cyclophosphamide therapy

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… Abbreviations: APAF-1, Apoptotic Protease Activating Factor 1; ATP, Adenosine triphosphate; BAD, BCL2 associated agonist of cell death; BAX, Bcl-2-associated X-protein; Caspase, cysteine-dependent, aspartate-specific peptidase; CoA, coenzyme A; COX-2, cyclooxygenase-2; CPT-1, Carnitine palmitoyltransferase …

Advances and clinical applications of immune checkpoint inhibitors in hematological malignancies.

Immune checkpoints are differentially expressed on various immune cells to regulate immune responses in tumor microenvironment. Tumor cells can activate the immune checkpoint pathway to establish an immunosuppressive tumor microenvironment and inhibit the anti-tumor immune response, which may lead to tumor progression by evading immune surveillance. Interrupting co-inhibitory signaling pathways with immune checkpoint inhibitors (ICIs) could reinvigorate the anti-tumor immune response and promote immune-mediated eradication of tumor cells. As a milestone in tumor treatment, ICIs have been first

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… bispecific antibody B and T lymphocyte attenuator classic Hodgkin lymphoma c‐myelocytomatosis viral oncogene homolog chimeric antigen receptor T‐cell cluster of differentiation conventional DCs cytokine‐induced killer checkpoint inhibitory T cell‐engaging chronic myeloid leukemia acetyl coenzyme … For example, a new study demonstrates that programmed cell death protein 1 (PD‐1) signaling inhibits T‐cell tumors by restricting the production of glycolytic energy and acetyl coenzyme A (CoA) in a mouse model of T‐cell non‐Hodgkin lymphoma (T‐NHL) and tumor cells from patients with T‐NHL [ 2 ]. …

National guidelines for diagnosis and treatment of osteoporosis in Slovakia.

BACKGROUND: Osteoporosis is a chronic, systemic skeletal disease characterized by decreased bone mass and microarchitectural deterioration, leading to increased fracture risk. In Slovakia, its prevalence is estimated at 6%, with substantial health, social, and economic burdens. OBJECTIVE: The Slovak national guideline provides an overview for the diagnosis, prevention, and treatment of osteoporosis in Slovakia, reflecting recent scientific advances and recommendations from international bodies. METHODS: The guidelines were developed by a multidisciplinary expert panel and officially adopted

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… The ability to inhibit bone resorption is based on interference with the enzyme activity of osteoclasts; they inhibit the enzyme farnesyl diphosphate synthase (synonym farnesyl pyrophosphate synthase ) in the 3-hydroxy- 3-methylglutaryl coenzyme A reductase pathway, important in the process of GTPase …

Chemotherapy-Mediated Complications of Wound Healing: An Understudied Side Effect.

Significance: Chemotherapy is a primary method to treat cancer. While chemotherapeutic drugs are designed to target rapidly dividing cancer cells, they can also affect other cell types. In the case of dermal cells and macrophages involved in wound healing, cytotoxicity often leads to the development of chronic wounds. The situation becomes even more severe when chemotherapy is combined with surgical tumor excision. Recent Advances: Despite its significant impact on patients' recovery from surgery, the issue of delayed wound healing in individuals undergoing chemotherapy remains inadequately ex

Association between Cholesterol Level and the Risk of Hematologic Malignancy According to Menopausal Status: A Korean Nationwide Cohort Study.

Recent studies have revealed the possible association between serum cholesterol levels and hematologic malignancy (HM). However, limited information is available about how reproductive factors interact with this association. Therefore, we investigated the roles of serum cholesterol in the risk of HM according to the menopausal status. We finally identified 1,189,806 premenopausal and 1,621,604 postmenopausal women who underwent a national health screening program in 2009 using data from the Korean National Health Insurance Service database. Overall, 5449 (0.19%) developed HM. Among postmenopau

Epigenetic and Genetic Keys to Fight HPV-Related Cancers.

Cervical cancer ranks as the fourth most prevalent cancer among women globally, with approximately 600,000 new cases being diagnosed each year. The principal driver of cervical cancer is the human papillomavirus (HPV), where viral oncoproteins E6 and E7 undertake the role of driving its carcinogenic potential. Despite extensive investigative efforts, numerous facets concerning HPV infection, replication, and pathogenesis remain shrouded in uncertainty. The virus operates through a variety of epigenetic mechanisms, and the epigenetic signature of HPV-related tumors is a major bottleneck in our

Study of Liposomes Containing Extract from the Leaves of Protium heptaphyllum (Aubl.) March in Animals Submitted to a Mutagenic Model Induced by Cyclophosphamide.

Cyclophosphamide (CPA) is an alkylating agent used as a chemotherapy agent in the treatment of cancer, but it has immunosuppressive effects. Protium heptaphyllum (P. heptaphyllum) is a plant rich in triterpenes and flavonoids, with some bioactive and therapeutic properties presented in the literature. Thus, the present study aimed to investigate the chemoprotective potential of P. heptaphyllum extract inserted into liposomes against oxidative damage chemically induced by CPA. Male Swiss mice received 1.5 mg/kg of P. heptaphyllum liposomes as a pre-treatment for 14 consecutive days (via gavage)

High-Dose Vitamin C for Cancer Therapy.

In recent years, the idea that Vitamin C (Vit-C) could be utilized as a form of anti-cancer therapy has generated many contradictory arguments. Recent insights into the physiological characteristics of Vit-C, its pharmacokinetics, and results from preclinical reports, however, suggest that high-dose Vit-C could be effectively utilized in the management of various tumor types. Studies have shown that the pharmacological action of Vit-C can attack various processes that cancerous cells use for their growth and development. Here, we discuss the anti-cancer functions of Vit-C, but also the potenti

Биоинформатический анализ взаимодействия миелинов и микробов говорит о том, что в патогенезе множественных склерозов присутствуют различные виды молекулярной имитации.

Множественный склероз (MS) — разрушительная аутоиммунная болезнь, приводящая к разрушению милиновой оболочки в центральной нервной системе человека (КНС). Было установлено, что инфекция вирусов и бактерий тесно связана с наступлением мороза или его остротой. Мы предположили, что атака иммунной системы на милиновую оболочку может быть спровоцирована вирусами и бактериальными антигенами, которые напоминают компоненты миелиновой оболочки. Для выявления вирусных и бактериальных антигенов, похожих на миелин олигодендроцит гликпротеин (МОГ) и миелинский основной протеин (МБП), был применен подход, о

Disturbing the Redox Balance Using Buthionine Sulfoximine Radiosensitized Somatostatin Receptor-2 Expressing Pre-Clinical Models to Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE.

Peptide receptor radionuclide therapy with 177Lu-DOTATATE improves the outcome of patients with somatostatin receptor (SSTR)-expressing neuroendocrine tumours. Nevertheless, stable disease has been the main response pattern observed, with some rare complete responses. Lu-177 exerts about two-thirds of its biological effects via the indirect effects of ionizing radiation that generate reactive oxygen species, eventually leading to oxidative damage and cell death. This provides a rationale for targeting the antioxidant defence system in combination with 177Lu-DOTATATE. In the present study, the

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… After 1 h incubation at 37 °C, the substrate (5,5′-dithiobis (2-nitrobenzoic acid)) (DTNB), coenzyme and enzyme (glutathione reductase) were added into the wells, followed by 10 min incubation at 37 °C. …

Convergent targeting of FUNDC1-dependent mitophagy sensitises and overcomes resistance to EGFR inhibition.

Combination therapies are critical for enhancing and prolonging the efficacy of EGFR inhibitors. Here, we uncover FUNDC1-dependent mitophagy as a key protective mechanism in EGFR-mutant non-small cell lung cancer (NSCLC). We discover that nitidine, a bioactive component of the traditional Xihuang Pill formulation, synergises with the EGFR inhibitor osimertinib. Mechanistically, nitidine and osimertinib synergistically disrupt FUNDC1-mediated mitophagy, leading to mitochondrial dysfunction and accumulation of reactive oxygen species in EGFR-mutant NSCLC. We further show that both osimertinib an

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… Cytosolic acetyl‐coenzyme A is a signalling metabolite to control mitophagy. Nature. 2026;649:1022‐1031. doi: 10.1038/s41586‐025‐09745‐x 30. Zhang W, Guo C, Li Y, et al. Mitophagy mediated by HIF‐1α/FUNDC1 signaling in tubular cells protects against renal ischemia/reperfusion injury. …

Virtual Screening of FDA-Approved Compounds: Exploring New Alternatives for HIV Treatment.

Human immunodeficiency virus (HIV) infection remains a significant public health challenge, particularly because of the emergence of drug-resistant strains against the drugs currently used in highly active antiretroviral therapy (HAART). The ongoing search for new molecules with therapeutic potential remains crucial. In this study, a virtual screening approach was employed to identify novel candidates with therapeutic potential for HIV. High-throughput screening (HTS) data were used to train and validate quantitative structure-activity relationship (QSAR) models, which were subsequently applie

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… Medications for Cardiovascular Conditions Fluvastatin (ZINC000001886617) is a hydroxymethylglutaryl-coenzyme A reductase inhibitor widely used to reduce plasma cholesterol levels. …

Animal Models in Rheumatoid Arthritis: Is There a Correlation Between Autoantibodies in Human Pathology and Animal Models?

RA is a chronic autoimmune disease characterized by synovial inflammation and joint damage, driven by autoantibodies such as ACPA, anti-CarP and RF. These autoantibodies, influenced by genetic and environmental factors, play a crucial role in RA pathogenesis through post-translational modifications like citrullination, carbamylation, and acetylation. The early detection of ACPA provides a potential window for intervention, while anti-CarP antibodies correlate with severe disease progression and RF aids in diagnosis. Translating these findings from human pathology to animal models presents sign

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… It involves the attachment of an acetyl group, donated by acetyl-coenzyme A, to either the N-terminus of proteins or to lysine residues. This process, facilitated by various N-terminal and lysine acetyltransferases, is reversible and can significantly impact protein function [ 34 ]. …

Cardiac toxicities in multiple myeloma: an updated and a deeper look into the effect of different medications and novel therapies.

With the continuous improvement in survival of cancer patients, including those with multiple myeloma, related to the novel treatment agents and therapeutic approaches, the probability for patients to develop cardiovascular disease has significantly increased, especially in elderly patients and those with additional risk factors. Multiple myeloma is indeed a disease of the elderly population and so these patients are, solely by age, at an increased risk of cardiovascular disease. Risk factors for these events can be patient-, disease- and/or therapy-related, and they have been shown to adverse

CXCL12/CXCR4 axis supports mitochondrial trafficking in tumor myeloma microenvironment.

Mesenchymal stromal cells (MSCs) within the protective microenvironment of multiple myeloma (MM) promote tumor growth, confer chemoresistance and support metabolic needs of plasma cells (PCs) even transferring mitochondria. In this scenario, heterocellular communication and dysregulation of critical signaling axes are among the major contributors to progression and treatment failure. Here, we report that myeloma MSCs have decreased reliance on mitochondrial metabolism as compared to healthy MSCs and increased tendency to deliver mitochondria to MM cells, suggesting that this intercellular exch

Morpholino-driven blockade of Dkk-1 in osteosarcoma inhibits bone damage and tumour expansion by multiple mechanisms.

BackgroundOsteosarcoma (OS) is the most common primary bone malignancy. Chemotherapy plays an essential role in OS treatment, potentially doubling 5-year event-free survival if tumour necrosis can be stimulated. The canonical Wnt inhibitor Dickkopf-1 (Dkk-1) enhances OS survival in part through upregulation of aldehyde-dehydrogenase-1A1 which neutralises reactive oxygen species originating from nutritional stress and chemotherapeutic challenge.MethodsA vivo morpholino (DkkMo) was employed to block the expression of Dkk-1 in OS cells. Cell mitosis, gene expression and bone destruction were meas

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… Douville J Beaulieu R Balicki D ALDH1 as a functional marker of cancer stem and progenitor cells Stem Cells Dev 2009 18 17 25 18573038 10.1089/scd.2008.0055 30. de Launoit Y Adamski J Unique multifunctional HSD17B4 gene product: 17beta-hydroxysteroid dehydrogenase 4 and D-3-hydroxyacyl-coenzyme A dehydrogenase …

Drug repurposing in malignant pleural mesothelioma: a breath of fresh air?

Drug repurposing is the use of known drugs for new indications. Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. So far, few treatments have been approved in this disease. However, its incidence is expected to increase significantly, particularly in developing countries. Consequently, drug repurposing appears as an attractive strategy for drug development in MPM, since the known pharmacology and safety profile based on previous approvals of repurposed drugs allows for faster time-to-market for patients and lower treatment cost. This is critical in low- and middle-in

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… Cerivastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, inhibits endothelial cell proliferation induced by angiogenic factors in vitro and angiogenesis in in vivo models. Arterioscler Thromb Vasc Biol 2002; 22: 623–629. 45. Denoyelle C, Vasse M, Körner M, et al. …

Посттрансляционные изменения в нейроиммунных клетках во время нейроинфламмации: комплексные сети регулирования и терапевтические возможности.

Нейроинфламмация представляет собой общий патологический механизм, лежащий в основе широкого спектра нарушений центральной нервной системы (КНС), включая нейродегенеративные расстройства (НДД), ишемический инсульт (ИС), травматическое повреждение мозга (ТБИ) и демиелионирующие заболевания, такие как множественный склероз (МС). Этот процесс начинается с организованной реакции микроглий, астроцитов, олигодендроцитов, нейронов, эндотелиальных клеток головного мозга и проникновения в периферийные иммунные клетки. Нейроинфламмация может облегчить ремонт тканей или, наоборот, увековечить хроническое

The underexplored links between cancer and the internal body climate: Implications for cancer prevention and treatment.

In order to effectively manage and cure cancer we should move beyond the general view of cancer as a random process of genetic alterations leading to uncontrolled cell proliferation or simply a predictable evolutionary process involving selection for traits that increase cell fitness. In our view, cancer is a systemic disease that involves multiple interactions not only among cells within tumors or between tumors and surrounding tissues but also with the entire organism and its internal "milieu". We define the internal body climate as an emergent property resulting from spatial and temporal in

Targeting fibrosis, mechanisms and cilinical trials.

Fibrosis is characterized by the excessive extracellular matrix deposition due to dysregulated wound and connective tissue repair response. Multiple organs can develop fibrosis, including the liver, kidney, heart, and lung. Fibrosis such as liver cirrhosis, idiopathic pulmonary fibrosis, and cystic fibrosis caused substantial disease burden. Persistent abnormal activation of myofibroblasts mediated by various signals, such as transforming growth factor, platelet-derived growth factor, and fibroblast growh factor, has been recongized as a major event in the occurrence and progression of fibrosi