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Lost in Translation (LiT): IUPHAR Review 6.

Translational medicine is a roller coaster with occasional brilliant successes and a large majority of failures. Lost in Translation 1 ('LiT1'), beginning in the 1950s, was a golden era built upon earlier advances in experimental physiology, biochemistry and pharmacology, with a dash of serendipity, that led to the discovery of many new drugs for serious illnesses. LiT2 saw the large-scale industrialization of drug discovery using high-throughput screens and assays based on affinity for the target molecule. The links between drug development and university sciences and medicine weakened, but t

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… The days of seeing a Paul Ehrlich magic bullet aimed at single disease target are not over but an era of pre‐designed, multi‐drug treatment is the way forward for translational medicine. …

The Clinical Application of Ozonetherapy

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Some Aspects and Convergence of Human and Veterinary Drug Repositioning.

Drug innovation traditionally follows a de novo approach with new molecules through a complex preclinical and clinical pathway. In addition to this strategy, drug repositioning has also become an important complementary approach, which can be shorter, cheaper, and less risky. This review provides an overview of drug innovation in both human and veterinary medicine, with a focus on drug repositioning. The evolution of drug repositioning and the effectiveness of this approach are presented, including the growing role of data science and computational modeling methods in identifying drugs with po

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… From Magic Bullets to Designed Multiple Ligands. Drug Discov. Today. 2004;9:641–651. doi: 10.1016/S1359-6446(04)03163-0. 50. Mátyus P., Rettegi T., Varró A., Papp J.G. New Antiarrhythmic Agents: A Conceptually Novel Approach. Med. Res. …

Theranostic Potentials of Gold Nanomaterials in Hematological Malignancies.

Hematological malignancies (HMs) are a heterogeneous group of blood neoplasia generally characterized by abnormal blood-cell production. Detection of HMs-specific molecular biomarkers (e.g., surface antigens, nucleic acid, and proteomic biomarkers) is crucial in determining clinical states and monitoring disease progression. Early diagnosis of HMs, followed by an effective treatment, can remarkably extend overall survival of patients. However, traditional and advanced HMs' diagnostic strategies still lack selectivity and sensitivity. More importantly, commercially available chemotherapeutic dr

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… Chapter 1—From the “Magic Bullet” to Advanced Nanomaterials for Active Targeting in Diagnostics and Therapeutics Biomedical Applications of Functionalized Nanomaterials Sarmento B. das Neves J. Elsevier Amsterdam, The Netherlands 2018 1 32 86. Roma-Rodrigues C. Fernandes A.R. Baptista P.V. …

Tumour-associated macrophages: versatile players in the tumour microenvironment.

Tumour-Associated Macrophages (TAMs) are one of the pivotal components of the tumour microenvironment. Their roles in the cancer immunity are complicated, both pro-tumour and anti-cancer activities are reported, including not only angiogenesis, extracellular matrix remodeling, immunosuppression, drug resistance but also phagocytosis and tumour regression. Interestingly, TAMs are highly dynamic and versatile in solid tumours. They show anti-cancer or pro-tumour activities, and interplay between the tumour microenvironment and cancer stem cells and under specific conditions. In addition to the c

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… Neutralizing tumour-promoting chronic inflammation: a magic bullet? Science 339 (6117), 286–291. 10.1126/science.1232227 Cowman S. J., Fuja D. G., Liu X. D., Tidwell R. S. S., Kandula N., Sirohi D., et al. (2020). Macrophage HIF-1α is an independent prognostic indicator in kidney cancer. Clin. …

A Comprehensive Review on the Therapeutic Potential of Curcuma longa Linn. in Relation to its Major Active Constituent Curcumin.

Curcuma longa Linn. (C. longa), popularly known as turmeric, belongs to the Zingiberaceae family and has a long historical background of having healing properties against many diseases. In Unani and Ayurveda medicine, C. longa has been used for liver obstruction and jaundice, and has been applied externally for ulcers and inflammation. Additionally, it is employed in several other ailments such as cough, cold, dental issues, indigestion, skin infections, blood purification, asthma, piles, bronchitis, tumor, wounds, and hepatic disorders, and is used as an antiseptic. Curcumin, a major constitu

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… Curcumin-a Magical Medicine: a Comprehensive Review. Int. ayurvedic Med. J. 5 (2), 458–467. Deshpande U. R., Gadre S. G., Raste A. S., Pillai D., Bhide S. V., Samuel A. M. (1998). Protective Effect of Turmeric (Curcuma Longa L.) Extract on Carbon Tetrachloride-Induced Liver Damage in Rats. …

Molecular targeted therapy for anticancer treatment.

Since the initial clinical approval in the late 1990s and remarkable anticancer effects for certain types of cancer, molecular targeted therapy utilizing small molecule agents or therapeutic monoclonal antibodies acting as signal transduction inhibitors has served as a fundamental backbone in precision medicine for cancer treatment. These approaches are now used clinically as first-line therapy for various types of human cancers. Compared to conventional chemotherapy, targeted therapeutic agents have efficient anticancer effects with fewer side effects. However, the emergence of drug resistanc

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… Brief history of molecular targeted therapy Paul Ehrlich first proposed the concept of targeted therapy in the 1890s as a “magic bullet” that would be completely specific for the target and thus safe without any additional toxicity 14 , 16 . …

The emerging role of exosomes in innate immunity, diagnosis and therapy.

Exosomes, which are nano-sized transport bio-vehicles, play a pivotal role in maintaining homeostasis by exchanging genetic or metabolic information between different cells. Exosomes can also play a vital role in transferring virulent factors between the host and parasite, thereby regulating host gene expression and the immune interphase. The association of inflammation with disease development and the potential of exosomes to enhance or mitigate inflammatory pathways support the notion that exosomes have the potential to alter the course of a disease. Clinical trials exploring the role of exo

Comparing the Therapeutic Potential of Stem Cells and their Secretory Products in Regenerative Medicine.

Cell therapy involves the transplantation of human cells to replace or repair the damaged tissues and modulate the mechanisms underlying disease initiation and progression in the body. Nowadays, many different types of cell-based therapy are developed and used to treat a variety of diseases. In the past decade, cell-free therapy has emerged as a novel approach in regenerative medicine after the discovery that the transplanted cells exerted their therapeutic effect mainly through the secretion of paracrine factors. More and more evidence showed that stem cell-derived secretome, i.e., growth fac

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… Systemic delivery of mesenchymal stem cells condition media in repeated doses acts as magic bullets in restoring IFN- γ /IL-4 balance in asthmatic rats Life Sciences 2018 212 30 36 10.1016/j.lfs.2018.09.049 2-s2.0-85054526366 30268855 125 Tan J. L. Lau S. N. Leaw B. …

Nanobodies for Medical Imaging: About Ready for Prime Time?

Recent advances in medical treatments have been revolutionary in shaping the management and treatment landscape of patients, notably cancer patients. Over the last decade, patients with diverse forms of locally advanced or metastatic cancer, such as melanoma, lung cancers, and many blood-borne malignancies, have seen their life expectancies increasing significantly. Notwithstanding these encouraging results, the present-day struggle with these treatments concerns patients who remain largely unresponsive, as well as those who experience severely toxic side effects. Gaining deeper insight into t

2,4 Dinitrophenol as Medicine.

In the sanctity of pure drug discovery, objective reasoning can become clouded when pursuing ideas that appear unorthodox, but are spot on physiologically. To put this into historical perspective, it was an unorthodox idea in the 1950's to suggest that warfarin, a rat poison, could be repositioned into a breakthrough drug in humans to protect against strokes as a blood thinner. Yet it was approved in 1954 as Coumadin® and has been prescribed to billions of patients as a standard of care. Similarly, no one can forget the horrific effects of thalidomide, prescribed or available without a prescri

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… It is not a “magical elixir”, but based upon the scientific fact that: 1) all human cells have mitochondria except mature red blood cells, 2) they have a symbiotic relationship within the cell governing cell survival and functions that impact many pathways, and 3) from experimental studies in so many …

Computational proteomics to enhance personalized treatment of COVID-19 and Long COVID.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to significant global health burden, including both acute infections and persistent post-acute sequelae, also known as Long COVID (LC) in survivors. While clinical management has reduced case-fatality rates, a substantial proportion of patients develop LC, a heterogeneous syndrome with long-term symptoms. This complex continuum requires therapeutic strategies for both the acute and chronic phases. Plasma proteomics has emerged as a powerful tool in precision medicin

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… A vital shift occurs from seeking a single “magic bullet” to developing synergistic combinations addressing viral factors and complex host-mediated pathologies contributing to LC. Antivirals are indicated for patients with viral persistence. …

Precision Medicine in Inflammatory Bowel Disease: A Spotlight on Emerging Molecular Biomarkers.

Inflammatory bowel diseases (IBD) remain challenging in terms of understanding their causes and in terms of diagnosing, treating, and monitoring patients. Modern diagnosis combines biomarkers, imaging, and endoscopic methods. Common biomarkers like CRP and fecal calprotectin, while invaluable tools, have limitations and are not entirely specific to IBD. The limitations of existing markers and the invasiveness of endoscopic procedures highlight the need to discover and implement new markers. With an ideal biomarker, we could predict the risk of disease development, as well as the possibility of

Myeloid Cell-Derived Arginase in Cancer Immune Response.

Amino acid metabolism is a critical regulator of the immune response, and its modulating becomes a promising approach in various forms of immunotherapy. Insufficient concentrations of essential amino acids restrict T-cells activation and proliferation. However, only arginases, that degrade L-arginine, as well as enzymes that hydrolyze L-tryptophan are substantially increased in cancer. Two arginase isoforms, ARG1 and ARG2, have been found to be present in tumors and their increased activity usually correlates with more advanced disease and worse clinical prognosis. Nearly all types of myeloid

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… Neutralizing tumor-promoting chronic inflammation: a magic bullet? Science . ( 2013 ) 339 : 286 – 91 . 10.1126/science.1232227 23329041 PMC3591506 10. Hibbs J Taintor R Vavrin Z . Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite . …

Review: Oncolytic virotherapy, updates and future directions.

Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or no

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… Limitations of oncolytic virotherapy OVs are not the ‘magic bullet’ for cancer therapy. Single agent activity is modest for most agents. The main limitation of oncolytic virotherapy is accurate delivery to the target. The ideal method of delivery is systemic, preferably intravenous (IV). …

Infectious Diseases

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Role of Proteins in Oncology: Advances in Cancer Diagnosis, Prognosis, and Targeted Therapy-A Narrative Review.

Modern oncology increasingly relies on the role of proteins as key components in cancer diagnosis, prognosis, and targeted therapy. This review examines advancements in protein biomarkers across several cancer types, including breast cancer, lung cancer, ovarian cancer, and hepatocellular carcinoma. These biomarkers have proven critical for early detection, treatment response monitoring, and tailoring personalized therapeutic strategies. The article highlights the utility of targeted therapies, such as tyrosine kinase inhibitors and monoclonal antibodies, in improving treatment efficacy while

Изучение связи между ядерными рецепторами в гематологических галереях.

Гематологические магнации (ГМ) представляют собой подмножество новообразований, затрагивающих кровь, костный мозг и лимфатические системы, которые в основном подразделяются на лейкемию, лимфому и множественную миелому. Их прогнозы значительно отличаются друг от друга, причем, несмотря на текущее лечение, часто возникает опасность рецидива. Несмотря на то, что современные терапевтические стратегии расширили общее выживание пациентов, они не предлагают лечения на продвинутых этапах и часто приводят к таким проблемам, как приобретение лекарственной устойчивости, рецидивы и серьезные побочные эффе

Iron Sucrose: A Wealth of Experience in Treating Iron Deficiency.

Iron deficiency and iron-deficiency anemia are associated with increased morbidity and mortality in a wide range of conditions. In many patient populations, this can be treated effectively with oral iron supplementation; but in patients who are unable to take or who do not respond to oral iron therapy, intravenous iron administration is recommended. Furthermore, in certain conditions, such as end-stage kidney disease, chronic heart failure, and inflammatory bowel disease, intravenous iron administration has become first-line treatment. One of the first available intravenous iron preparations i

Coexistence of Autoantibodies against the Golgi Complex and Ro52 Antigen in a Patient with Nonspecific Interstitial Pneumonia.

Nonspecific interstitial pneumonia (NSIP) is often associated with connective tissue diseases (CTD). The diagnosis of NSIP was confirmed in a 63-year-old man by high-resolution computed tomography and an open lung biopsy. Anti-Golgi complex autoantibodies (AGA) and anti-Ro52 antibodies were simultaneously detected at high concentrations. Autoantibodies to aminoacyl-tRNA synthetases (ARS) were negative. The patient was treated with corticosteroids for six months. During the seven-year follow-up, NSIP had a slow progression and patient had not developed the clinical features of CTD. The present