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Marine Natural Products, Multitarget Therapy and Repurposed Agents in Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial disease characterized by the presence of amyloid plaques, neurofibrillary tangles, and nerve cell death that affects, mainly, older people. After decades of investigation, the search for an efficacious treatment for AD remains and several strategies can be and are being employed in this journey. In this review, four of the most promising strategies, alongside with its most promising agents under investigation or development are highlighted. Marine natural products (MNP) are a source of unique chemical structures with useful biological activities for

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… In vivo, clioquinol caused a reduction of amyloid deposits [ 114 ]. Evidence suggests that diabetes and related features, such as insulin resistance, increase the risk of AD. As a result of this, antidiabetic treatments may be useful for AD treatment [ 140 ]. … Clioquinol: Review of its mechanisms of action and clinical uses in neurodegenerative disorders CNS Neurosci. 2012 18 41 46 10.1111/j.1755-5949.2010.00231.x PMC6493473 21199452 135. Campbell J.M. Stephenson M.D. de Courten B. Chapman I. Bellman S.M. Aromataris E. …

Downregulation of SLC40A1 leads to iron accumulation in fibrotic lung fibroblasts.

Iron is an essential nutrient for almost all organisms. However, excess iron generates reactive oxygen species and causes tissue injuries. Iron is implicated in idiopathic pulmonary fibrosis (IPF). In this study, we examined iron accumulation in fibrotic lung fibroblasts and the underlying mechanisms. We hypothesize that the downregulation of Solute Carrier Family 40 Member 1 (SLC40A1) results in iron accumulation in lung fibroblasts of IPF patients. Using a Prussian Blue iron staining, we found that iron accumulated in the fibrotic region of the lungs from IPF patients and bleomycin- and asbe

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… Several reports have shown that the bleomycin-induced lung fibrosis in mice is reduced by iron depletion using deferoxamine administered intranasally or clioquinol administered orally [ 6 – 8 ]. … Clioquinol attenuates pulmonary fibrosis through inactivation of fibroblasts via iron chelation. Am J Respir Cell Mol Biol. 2021;65(2):189–200. 8. Pei Z, Qin Y, Fu X, Yang F, Huo F, Liang X, et al. Inhibition of ferroptosis and iron accumulation alleviates pulmonary fibrosis in a bleomycin model. …

Drug Repurposing for Cancer Treatment: A Comprehensive Review.

Cancer ranks among the primary contributors to global mortality. In 2022, the global incidence of new cancer cases reached about 20 million, while the number of cancer-related fatalities reached 9.7 million. In Saudi Arabia, there were 13,399 deaths caused by cancer and 28,113 newly diagnosed cases of cancer. Drug repurposing is a drug discovery strategy that has gained special attention and implementation to enhance the process of drug development due to its time- and money-saving effect. It involves repositioning existing medications to new clinical applications. Cancer treatment is a therap

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… Clioquinol, another anti-parasitic drug, has demonstrated anticancer properties by down-regulating HDAC expression in leukemia and malignant myeloma cells. It induces apoptosis by down-regulating HDAC and causing mitotic arrest, leading to p53 and p21 expression [ 75 , 76 ]. 2.1.4. … Tubulin polymerization | Preclinical | [ 62 , 63 , 64 , 69 , 70 , 71 , 72 , 172 , 173 ] Niclosamide | | Colon, prostate, liver, ovarian, and breast cancers | Wnt/β-catenin, NF-KB, mTOR, and JAK/STAT3 pathways | Uncoupling of oxidative phosphorylation | Preclinical | [ 66 , 73 , 74 , 162 , 163 , 164 ] Clioquinol …

What Drives Innovation: The Canadian Touch on Liposomal Therapeutics.

Liposomes are considered one of the most successful drug delivery systems (DDS) given their established utility and success in the clinic. In the past 40⁻50 years, Canadian scientists have made ground-breaking discoveries, many of which were successfully translated to the clinic, leading to the formation of biotech companies, the creation of research tools, such as the Lipex Extruder and the NanoAssemblr™, as well as contributing significantly to the development of pharmaceutical products, such as Abelcet®, MyoCet®, Marqibo®, Vyxeos®, and Onpattro™, which are making positive impacts on patient

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… The Bally group and Cuprous validated the concept of metal-dependent anticancer activity for copper-coordinating compounds through an in vitro screen on platinum-sensitive and platinum-resistant cell lines and prepared injectable copper-based formulations of DDC and clioquinol [ 80 , 89 , 90 ]. … Development of a copper-clioquinol formulation suitable for intravenous use Drug Deliv. Transl. Res. 2018 8 239 251 10.1007/s13346-017-0455-7 29247315 PMC5756275 91. Prosser K.E. Leung A.W. Harrypersad S. Lewis A.R. Bally M.B. Walsby C.J. …

Cuproptosis Inducers in Cancer Therapy: State of the Art and Challenges.

Cancer continues to be the primary cause of death despite significant progress in medicine, and finding effective therapies remains a challenge. New treatments are needed to minimize the harmful effects on the body and increase the selectivity of drugs. These therapies must also overcome cancer cell resistance and prevent metastasis. Metal-based drugs are becoming increasingly crucial for treating tumors, and copper ion-based systems and nanoparticles have been identified as having unique properties and anticancer potential. Given the key role exerted by Cu in the etiology, severity, and progr

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… Unlike other ionophores such as clioquinol (CQ), inductively coupled plasma (ICP)‐MS analysis showed that UM4118 is a selective Cu ionophore as it selectively increases intracellular Cu without significantly affecting iron or zinc. …

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

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… Obermajer N Novel mechanism of cathepsin B inhibition by antibiotic nitroxoline and related compounds ChemMedChem 2011 6 1351 6 21598397 10.1002/cmdc.201100098 70 Jiang H Taggart JE Zhang X Benbrook DM Lind SE Ding WQ Nitroxoline (8-hydroxy-5-nitroquinoline) is more a potent anti-cancer agent than clioquinol …

Guideline "diagnosis and non interventional therapy of neuropathic pain" of the German Society of Neurology (deutsche Gesellschaft für Neurologie).

2019 the DGN (Deutsche Gesellschaft für Neurology) published a new guideline on the diagnosis and non-interventional therapy of neuropathic pain of any etiology excluding trigeminal neuralgia and CRPS (complex regional pain syndrome). Neuropathic pain occurs after lesion or damage of the somatosensory system. Besides clinical examination several diagnostic procedures are recommended to assess the function of nociceptive A-delta and C-Fibers (skin biopsy, quantitative sensory testing, Laser-evoked potentials, Pain-evoked potentials, corneal confocal microscopy, axon reflex testing). First line

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… vitamin deficiency (especially vitamin B12) Medication Antiretroviral therapy, chemotherapy (cisplatin, oxaliplatin, Taxanes, thiouracil, vincristine), disulfiram, antibiotics (ethambutol, isoniazid, nitrofurantoin, chloramphenicol, metronidazole), thalidomide, gold Toxins alcohol, acrylamid, arsenic, clioquinol …

Adhesion molecules in multiple myeloma oncogenesis and targeted therapy.

Every day we march closer to finding the cure for multiple myeloma. The myeloma cells inflict their damage through specialized cellular meshwork and cytokines system. Implicit in these interactions are cellular adhesion molecules and their regulators which include but are not limited to integrins and syndecan-1/CD138, immunoglobulin superfamily cell adhesion molecules, such as CD44, cadherins such as N-cadherin, and selectins, such as E-selectin. Several adhesion molecules are respectively involved in myelomagenesis such as in the transition from the precursor disorder monoclonal gammopathy of

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… anti-CD138, anti-BCMA, anti-SLAM7 CAR—T cells | Chimeric antigen receptor (CAR) T cells Venetoclax | BCL-2 inhibitor DANFIN | NF-κB inhibitor Sorafenib, Vemurafenib, Cobimetinib, Selumetinib | RAS/RAF/MEK/ERK inhibitors Palbociclib | CDK4/6 inhibitor Dovitinib, BGJ398, MFGR1877S, AZD4547 | FGFR inhibitors Clioquinol …

Restoring the Immunity in the Tumor Microenvironment: Insights into Immunogenic Cell Death in Onco-Therapies.

Immunogenic cell death (ICD) elicited by cancer therapy reshapes the tumor immune microenvironment. A long-term adaptative immune response can be initiated by modulating cell death by therapeutic approaches. Here, the major hallmarks of ICD, endoplasmic reticulum (ER) stress, and damage-associated molecular patterns (DAMPs) are correlated with ICD inducers used in clinical practice to enhance antitumoral activity by suppressing tumor immune evasion. Approaches to monitoring the ICD triggered by antitumoral therapeutics in the tumor microenvironment (TME) and novel perspective in this immune sy

Recent Advances in Therapeutics for the Treatment of Alzheimer's Disease.

The most prevalent chronic neurodegenerative illness in the world is Alzheimer's disease (AD). It results in mental symptoms including behavioral abnormalities and cognitive impairment, which have a substantial financial and psychological impact on the relatives of the patients. The review discusses various pathophysiological mechanisms contributing to AD, including amyloid beta, tau protein, inflammation, and other factors, while emphasizing the need for effective disease-modifying therapeutics that alter disease progression rather than merely alleviating symptoms. This review mainly covers m

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… Synthesis and evaluation of clioquinol-rolipram/roflumilast hybrids as multitarget-directed ligands for the treatment of Alzheimer’s disease Eur. J. Med. Chem. 2019 163 512 526 30553143 10.1016/j.ejmech.2018.12.013 180. Hasan N. Zameer S. Najmi A.K. Parvez S. Akhtar M. …

Role of Nanomedicine-Based Therapeutics in the Treatment of CNS Disorders.

Central nervous system disorders, especially neurodegenerative diseases, are a public health priority and demand a strong scientific response. Various therapy procedures have been used in the past, but their therapeutic value has been insufficient. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier is two of the barriers that protect the central nervous system (CNS), but are the main barriers to medicine delivery into the CNS for treating CNS disorders, such as brain tumors, Parkinson's disease, Alzheimer's disease, and Huntington's disease. Nanotechnology-based medicinal

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… | amyloid-β inhibitor | [ 140 ] PNP | GBM | Anticancer | AS14111 aptamer Transferrin Pep-1 Angiopep | Enhance efficiency and anti-glioma | [ 141 , 142 , 143 , 144 , 145 ] PD | PD treatment | ApoE | Enhance the neuroprotective efficiency | [ 146 , 147 , 148 , 149 ] AD | AD treatment PET | ApoE 125 I-clioquinol …

Colorectal Cancer at the Crossroads: The Good, the Bad, and the Future of Platinum-Based Drugs.

Colorectal cancer (CRC) remains a significant global health challenge, ranking third in incidence and second in mortality among cancers worldwide. This review addresses the complex landscape of CRC, focusing on incidence, mortality trends, preventive strategies, and the evolving therapeutic approaches, particularly highlighting the role of platinum-based drugs like oxaliplatin (OXP). It also underscores the increasing burden of CRC, with factors such as westernized diets, aging populations, and genetic predispositions contributing to its prevalence. Therapeutically, early detection greatly enh

UEG Week 2017 Oral Presentations

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