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Validation of a data-driven multicomponent T2 analysis for quantifying myelin content in the cuprizone mouse model of multiple sclerosis.

BACKGROUND: Myelin quantification is essential for understanding a wide range of neurodegenerative pathologies. Voxel-wise multicomponent T2 (mcT2) analysis is the common approach for this purpose, yet no gold standard technique exist that can overcome the ambiguity of fitting several T2 components to a single-voxel signal. This challenge is further exacerbated in preclinical scan settings due to the addition of spurious diffusion encoding, resulting from the use of imaging gradients that are at least an order of magnitude larger than on typical clinical scanners. PURPOSE: Assess the utility

A Novel Hydroxamic Acid-Based Curcumin Derivative as Potent Histone Deacetylase Inhibitor for the Treatment of Glioblastoma.

Glioblastoma (GBM) is one of the most common primary and deadliest malignant brain tumor with chemoresistance and poor prognosis. There is a lack of effective chemotherapeutic drug for the treatment of GBM. In this work, we reported the preparation of a histone deacetylase (HDAC) inhibitor, DMC-HA, from the structural modification of natural product curcumin. DMC-HAs were tested in an HDAC inhibition assay and an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cytotoxicity. It showed potent inhibition of HDAC1-2 and HDAC6 with IC50 values in the submicromolar conce

Decoding iron deficiency in cancer: mechanisms, immune modulation, and therapeutic potential.

Iron is a vital micronutrient in many biological functions, including DNA metabolism, oxygen transport, and cellular energy generation. In this context, it is intimately linked to cancer biology. However, although many studies have comprehensively investigated and reviewed the effects of excess iron on tumor initiation and progression, the potential interrelations of iron deficiency with tumors have been largely neglected and need to be better defined. Recent studies have highlighted the complex relationship between iron deficiency and tumor biology. Iron deficiency in specific tumor types can

The Potential of Chronotherapy and Nanotherapy-Based Strategies for Glioblastoma Treatment.

Glioblastoma is the most common and aggressive brain tumour in adults, and despite ongoing efforts, effective treatment remains limited. Standard therapies often face challenges because of the tumour's specific biology, its aggressive nature, and the presence of certain physiological barriers in the brain that impede chemotherapeutics from reaching their target. Emerging research in circadian biology highlights the role of the internal circadian clock in tumour progression and treatment response. Evidence suggests that aligning therapy to patients' chronotypes could potentially improve treatme

Recent advances in drug repositioning for the discovery of new anticancer drugs.

Drug repositioning (also referred to as drug repurposing), the process of finding new uses of existing drugs, has been gaining popularity in recent years. The availability of several established clinical drug libraries and rapid advances in disease biology, genomics and bioinformatics has accelerated the pace of both activity-based and in silico drug repositioning. Drug repositioning has attracted particular attention from the communities engaged in anticancer drug discovery due to the combination of great demand for new anticancer drugs and the availability of a wide variety of cell- and targ

Covalent targeting of PSMD14 by Eupalinolide B induces oncoprotein degradation and apoptosis in acute promyelocytic leukemia cells.

Treatment of acute promyelocytic leukemia (APL) remains challenged by toxicities associated with current regimens, highlighting the need for novel and safer therapeutic agents. Here, we identify Eupalinolide B (EB), a natural sesquiterpene lactone isolated from Eupatorium lindleyanum DC., as a potent anti-leukemic compound targeting the human APL-derived HL-60 cell line. Through integrated chemoproteomic profiling and functional validation, we demonstrate that EB covalently binds and inhibits 26S proteasome non-ATPase regulatory subunit 14 (PSMD14), a deubiquitinase enzyme (DUB) within the 19S

Synthesis and biological evaluation of a new polymeric conjugate and nanocarrier with osteotropic properties.

Bone-seeking (osteotropic) drug delivery systems (ODDS) represent an interesting solution for targeting different types of drugs to the bones. In particular, anticancer and antibacterial agents could take advantage of such therapeutic strategy. We have recently developed an innovative approach to this aim: a new osteotropic biomaterial was prepared, based on the conjugation of a poly(lactide-co-glycolide) (PLGA) with the bisphosphonate drug alendronate (PLGA-ALE); its hemo- and cytocompatibility were verified. Starting with this copolymer, an osteotropic nanoparticle system (NP) was produced f

Protocol for the TMaC Study: A Patient-Blinded, Randomised, Sham-Controlled, Parallel-Group Study Evaluating Effects of Repetitive Transcranial Magnetic Stimulation on Chronic Chemotherapy-Induced Pain in Bowel Cancer Patients.

IntroductionChemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating consequence for people undergoing treatment for cancer, especially bowel cancer. Painful CIPN contributes to psychological distress, functional decline and reduced quality of life. Additionally, it is a dose-limiting factor for anticancer agents, compromising chemotherapy effectiveness and patient survival. To date, no effective long-term management options exist for painful CIPN. Whilst evidence suggests analgesic effects of repetitive transcranial magnetic stimulation (rTMS), little is known regarding

Companion Diagnostics in Clinical Therapy: Current Applications and Future Directions.

Companion diagnostics (CDx) plays a pivotal role in precision medicine by enabling personalized treatment plans based on individual biomarker profiles. This approach can enhance therapeutic efficacy in selected indications and may reduce healthcare expenditures. Particularly in oncology, precision targeted therapies targeting pathways such as EGFR, HER2, and programmed death-1/programmed death-ligand 1 have established robust models for biomarker-driven treatment. However, rapid advancements in diagnostic technologies, expanding application scopes, and increasingly complex mechanisms of biomar

Advanced multifunctional thermo- and electro-stimulative hydrogels for bone regeneration.

Bone defects caused by trauma, infection, tumors, osteoporosis, and diabetes disrupt skeletal integrity and impair regeneration. The healing process involves inflammatory hematoma formation, callus development, and remodeling, coordinated by diverse cells and signaling pathways. Conventional grafts and inorganic implants are limited by donor scarcity, immune rejection, and low bioactivity, necessitating more effective repair strategies. Recently, multifunctional smart hydrogels have emerged as a frontier in bone regeneration due to their biocompatibility, tunable structure, and ability to inte

How to Use a Prioritised Approach for Treating Hematological Disorders During the COVID-19 Pandemic in India?

The current pandemic coronavirus, SARS-CoV-2, is known to cause severe infection (COVID-19) in patients with comorbidities, particularly cancer or an immunosuppressed state. Most healthcare systems in the country are likely to be overwhelmed soon if the pandemic moves to a stage of community transmission. Currently, limited evidence is available for managing patients with hematological disorders during the COVID-19 pandemic. The current review summarises the possible challenges clinicians are likely to face, key considerations to guide decision making, and possible solutions to the anticipated

Crosstalk of thioredoxin system and programmed cell death: from pathophysiology to novel therapy.

The thioredoxin (Trx) system, an integral component of cellular redox regulation, preserves protein dithiol-disulfide equilibrium through its conserved Cys-Gly-Pro-Cys active site and is involved in key cellular functions, including cell proliferation, apoptosis, and signal transduction. In cancer biology, the thioredoxin system plays dual roles: overexpression can suppress oxidative stress and promote tumor growth, whereas dysfunction can trigger programmed cell death (PCD). However, a critical area for future research is to delineate how Trx modulates the intricate networks of PCD, and to id

Совпадение в полном тексте источника
… Iron chelation therapy has been shown to benefit multiple clinical endpoints in MDS, an effect at least partially attributed to the mitigation of iron-induced oxidative stress by chelators [ 310 ]. …

Lenalidomide: a brief review of its therapeutic potential in myelodysplastic syndromes.

Lenalidomide is a novel thalidomide analogue with enhanced immunomodulatory and antiangiogenic action lacking most of the typical thalidomide-associated adverse events. In myelodysplastic syndromes (MDS), it has been used primarily in the IPSS low- and intermediate-1 risk setting. Several trials have demonstrated its potential to lead to both erythroid and cytogenetic responses in these disease groups. In a clinical trial of patients with a del(5q) chromosomal abnormality, lenalidomide treatment resulted in red blood cell (RBC) transfusion independence in 67% of patients. Moreover, 45% of pati

Role of phytoconstituents in the management of COVID-19.

BackgroundCOVID-19, a severe global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged as one of the most threatening transmissible disease. As a great threat to global public health, the development of treatment options has become vital, and a rush to find a cure has mobilized researchers globally from all areas.Scope and approachThis review focuses on deciphering the potential of different secondary metabolites from medicinal plants as therapeutic options either as inhibitors of therapeutic targets of SARS-CoV-2 or as blockers of viral particles entry

Identification of iron metabolism-related predictive markers of endometriosis and endometriosis-relevant ovarian cancer.

Endometriosis is associated with ovarian cancers, mainly endometrioid and clear-cell carcinomas. Iron metabolism has been shown to play a role in endometriosis. Therefore, it is vital to explore the relationship between iron metabolism and ovarian cancer and to identify novel markers for diagnostics and therapeutics. The endometriosis dataset GSE51981 and the ovarian cancer dataset GSE26712 were obtained from the gene expression omnibus database, and differentially expressed genes were identified. Iron metabolism genes were obtained from molecular signatures database, and hub genes from the 3

Сенсорность клеток в глиальных клетках: последствия для множественного склероза.

Старение является наиболее распространенным фактором риска для развития заболевания множественным склерозом (MS). Клеточная сенсация, необратимое состояние остановки клеточного цикла, является основным фактором старения и, как было установлено, накапливается преждевременно в нейродегенеративных заболеваниях, включая болезнь Альцгеймера и Паркинсона. В последнее время внимание привлекает клеточная сенсация в центральной нервной системе пациентов MS, при этом ряд исследований свидетельствуют о том, что демиелинация вызывает клеточную сенесценцию с общими признаками p16INK4A и p21 выражения, окис

Двойная роль микроглии в множественном склерозе и его последствия для диагностики и ремонта.

Микроглия играет ключевую роль в развитии, иммунной слежке и восстановлении центральной нервной системы. Эти клетки играют многогранную роль в множестве склероза (MS), при этом есть основания полагать, что микроглия может способствовать как активному воспалению, так и воспалению. Например, было продемонстрировано, что микроглия может поддерживать разработку олигодендроцитов и фигоцитоза миелиновых обломков, способствуя тем самым надлежащему восстановлению. Однако чрезмерная активация микроглии в повреждениях MS усугубляет нейроинфламму, высвобождая подстрекательские цитокины и облегчая активац

Chemotherapy-induced neuropathies-a growing problem for patients and health care providers.

IntroductionChemotherapy-induced neuropathies are one of the most common side effects of cancer treatment, surpassing bone marrow suppression and kidney dysfunction. Chemotherapy effects on the nervous system vary between different classes of drugs and depend on specific chemical and physical properties of the drug used. The three most neurotoxic classes of anti-cancer drugs are: platinum-based drugs, taxanes, and thalidomide and its analogs; other, less neurotoxic but also commonly used drugs are: bortezomib, ixabepilone, and vinca alkaloids.MethodsHere, in this paper, based on our experience

Clinical practice guidelines on addressing cognitive impairment in treatable dementias.

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… Chelation therapy helps speed up recovery from heavy metal poisoning. …

Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets.

The onerous health and economic burden associated with head and neck squamous cell carcinoma (HNSCC) is a global predicament. Despite the advent of novel surgical techniques and therapeutic protocols, there is an incessant need for efficacious diagnostic and therapeutic targets to monitor the invasion, metastasis and recurrence of HNSCC due to its substantial morbidity and mortality. The differential expression patterns of histone deacetylases (HDACs), a group of enzymes responsible for modifying histones and regulating gene expression, have been demonstrated in neoplastic tissues. However, th