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A year in pharmacology: new drugs approved by the US food and drug administration in 2025.

The US Food and Drug Administration approved 45 new drugs and 4 new cellular and gene therapy products in 2025, that is, a total of 49 new medical therapies. Oncology, hematology/immunotherapy, and cardiovascular/respiratory drugs remain most frequent. Among oncology drugs, there is a trend for targeting ever smaller subtypes of malignancies and/or rarer malignancies. Trends over the past 6 years include steady levels of first-in-indication (about 10%), first-in-class (about 38%), and next-in-class (about 51%) approvals. Along with a large share of approvals in orphan indications (> 50%), fast

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… Silencing apoC-III relieves inhibition of lipoprotein lipase and enhances hepatic clearance of triglyceride-rich lipoproteins, resulting in sustained reductions in triglycerides, very-low-density lipoprotein, and chylomicrons. …

The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.

The cGAS-STING pathway acts as a critical molecular hub connecting genomic instability with cellular senescence. Functioning as a key regulator of the innate immune system, this pathway detects aberrant cytoplasmic DNA to activate downstream inflammatory responses, thereby playing a pivotal role in aging-related diseases. This review systematically explores the core mechanisms by which the cGAS-STING pathway regulates cellular senescence, emphasizing its role in triggering senescence through the recognition of DNA damage signals (e.g., oxidative stress, telomere dysfunction) and promoting para

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant atten

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… Sortilin/Neurotensin Receptor-3 Binds and Mediates Degradation of Lipoprotein Lipase. J. Biol. Chem. 1999;274:8832–8836. doi: 10.1074/jbc.274.13.8832. 51. Tang W., Lu Y., Tian Q.-Y., Zhang Y., Guo F.-J., Liu G.-Y., Syed N.M., Lai Y., Lin E.A., Kong L., et al. …

Body shape phenotypes of multiple anthropometric traits and cancer risk: a multi-national cohort study.

BackgroundClassical anthropometric traits may fail to fully represent the relationship of weight, adiposity, and height with cancer risk. We investigated the associations of body shape phenotypes with the risk of overall and site-specific cancers.MethodsWe derived four distinct body shape phenotypes from principal component (PC) analysis on height, weight, body mass index (BMI), waist (WC) and hip circumferences (HC), and waist-to-hip ratio (WHR). The study included 340,152 men and women from 9 European countries, aged mostly 35-65 years at recruitment (1990-2000) in the European Prospective I

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… One hypothesis is that HC tracks with gluteofemoral fat accumulation, which is associated with a more favourable adipokine profile and increased lipoprotein lipase activity [ 35 ], profiles that have been linked to lower endometrial cancer risk [ 36 ]. …

Nuclear Heparanase Regulates Chromatin Remodeling, Gene Expression and PTEN Tumor Suppressor Function.

Heparanase (HPSE) is an endoglycosidase that cleaves heparan sulfate and has been shown in various cancers to promote metastasis, angiogenesis, osteolysis, and chemoresistance. Although heparanase is thought to act predominantly extracellularly or within the cytoplasm, it is also present in the nucleus, where it may function in regulating gene transcription. Using myeloma cell lines, we report here that heparanase enhances chromatin accessibility and confirm a previous report that it also upregulates the acetylation of histones. Employing the Multiple Myeloma Research Foundation CoMMpass datab

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… Endothelial cell heparanase taken up by cardiomyocytes regulates lipoprotein lipase transfer to the coronary lumen after diabetes Diabetes 2014 63 2643 2655 10.2337/db13-1842 24608441 24. Wang F. Wang Y. Zhang D. Puthanveetil P. Johnson J.D. Rodrigues B. …

Systemic Lupus Erythematosus in Primary Care: An Update and Practical Messages for the General Practitioner.

Systemic Lupus Erythematosus (SLE) is a complex chronic autoimmune disease that manifests a wide range of organ involvement. Traditionally, the diagnosis and management of SLE is provided at secondary and tertiary centers to ensure prompt initiation of treatment, adequate control of flares and prevention of irreversible organ damage. Notwithstanding, the role of primary care in SLE is also emerging as there are still significant unmet needs such as the diagnostic delay at the community level and the high burden of therapy- and disease-related comorbidities. In the present review, we summarize

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… Numerous mechanisms are implicated in its pathogenesis, including antibodies against lipoprotein lipase as well as cytokines that affect the balance and content of lipoproteins ( 134 ). Prevalence of diabetes ranges from 2.7 to 7% and increases over time after diagnosis reaching up to 14% ( 135 ). …

EU Regulatory Pathways for ATMPs: Standard, Accelerated and Adaptive Pathways to Marketing Authorisation.

Advanced therapy medicinal products (ATMPs) require evaluation by the European Medicines Agency's Committee for Advanced Therapies prior to being placed on the European market, subject to a Marketing Authorisation granted by the European Commission. In common with other medicinal products, various regulatory pathways are available for taking ATMPs through clinical trials to market authorisation, and the regulatory pathway taken will depend on a product's characteristics and the target patient population. With the industry poised to deliver more late-stage clinical and commercial ATMPs for seri

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… lipase deficiency (LPLD) and severe or multiple pancreatitis attacks despite dietary fat restrictions; the diagnosis of LPLD has to be confirmed by genetic testing; the indication is restricted to patients with detectable levels of LPL protein | MA under exceptional circumstances orphan medicinal product … Indeed, uniQure’s Glybera, an orphan medicinal product and the first non-cell-based GTMP to be licensed globally, was authorised in 2012 under exceptional circumstances based on the extremely low prevalence of lipoprotein lipase deficiency (LPLD), a rare autosomal recessive inherited condition with a …

The Dynamic Role of Curcumin in Mitigating Human Illnesses: Recent Advances in Therapeutic Applications.

Herbal medicine, particularly in developing regions, remains highly popular due to its cost-effectiveness, accessibility, and minimal risk of adverse effects. Curcuma longa L., commonly known as turmeric, exemplifies such herbal remedies with its extensive history of culinary and medicinal applications across Asia for thousands of years. Traditionally utilized as a dye, flavoring, and in cultural rituals, turmeric has also been employed to treat a spectrum of medical conditions, including inflammatory, bacterial, and fungal infections, jaundice, tumors, and ulcers. Building on this longstandin

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… Additionally, curcumin administration at 300 mg/kg for three months in diabetic obese patients significantly reduced fasting blood sugar, insulin resistance, HbA1c, serum triglycerides, and free fatty acids (FFAs), while increasing lipoprotein lipase activity, highlighting its efficacy in lipid metabolism …

Nanoparticle-Based Drug Delivery System: A Patient-Friendly Chemotherapy for Oncology.

Chemotherapy is widely used to treat cancer. The toxic effect of conventional chemotherapeutic drugs on healthy cells leads to serious toxic and side effects of conventional chemotherapy. The application of nanotechnology in tumor chemotherapy can increase the specificity of anticancer agents, increase the killing effect of tumors, and reduce toxic and side effects. Currently, a variety of formulations based on nanoparticles (NPs) for delivering chemotherapeutic drugs have been put into clinical use, and several others are in the stage of development or clinical trials. In this review, after b

Different origin-derived exosomes and their clinical advantages in cancer therapy.

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the "golden communicators" between cells, can be designed to deliver different drugs, aiming to ac

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… Cheng et al. reported the proteomic and lipidomic analysis of exosomes derived from ovarian cancer cells (SKOV-3) and ovarian surface epithelial cells (HOSEPiC) and found that Cholesterol Ester (ChE), Zymosterol (ZyE), V collagen alpha 2 chain (COL5A2) and lipoprotein lipase (LPL) than from HOSEPiC usually …

Targeted protein degradation: advances in drug discovery and clinical practice.

Targeted protein degradation (TPD) represents a revolutionary therapeutic strategy in disease management, providing a stark contrast to traditional therapeutic approaches like small molecule inhibitors that primarily focus on inhibiting protein function. This advanced technology capitalizes on the cell's intrinsic proteolytic systems, including the proteasome and lysosomal pathways, to selectively eliminate disease-causing proteins. TPD not only enhances the efficacy of treatments but also expands the scope of protein degradation applications. Despite its considerable potential, TPD faces chal

Recent Progress of CircRNAs in Hematological Malignancies.

Circular RNAs (circRNAs) are now recognized as key regulators in the epigenetic control of genetic expression, being involved in a wide range of cellular activities such as proliferation, differentiation, and apoptosis. Their unique closed-loop structure endows them with stability and resistance to exonuclease degradation, making them not only key regulatory molecules within the cell but also promising biomarkers for disease diagnosis and prognosis, particularly in hematological malignancies. This review comprehensively explores the role of circRNAs in the pathogenesis, progression, and therap

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… CircRIC8B acted as a sponge for miR-199b-5p, preventing it from reducing lipoprotein lipase (LPL) mRNA levels. Furthermore, ezetimibe inhibited the development of CLL cells and reduced LPL mRNA expression 93 . …

Gene therapy of rare diseases as a milestone in medicine - overview of the field and report on initial experiences in Slovenia.

Gene therapy has transitioned from a long-awaited promise to a clinical reality, offering transformative treatments for rare congenital diseases and certain cancers, which have a significant impact on patients' lives. Current approaches focus on gene replacement therapy, either in vivo or ex vivo, mostly utilizing viral vectors to deliver therapeutic genes into target cells. However, refining these techniques is essential to overcome challenges and complications associated with gene therapy to ensure long-term safety and efficacy. Slovenia has witnessed significant advancements in this field s

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… In Europe, in 2012, the first gene therapy for lipoprotein lipase deficiency (Glybera, uniQure) obtained market authorization (while already in 2004 it obtained orphan drug status), an exceedingly rare metabolic disorder leading to severely elevated triglyceride levels and heightened risk of acute and …

Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance.

We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced pancreatitis (HCa-P), MEN1 (multiple endocrine neoplasia)-related neuroendocrine tumors (NETs), and insulin resistance (IR). This was a comprehensive review conducted via a PubMed search between January 2020 and January 2024. HCa-P (n = 9 studies, N = 1375) involved as a starting point parathyroid NETs (n = 7) or pancreatitis (n = 2, N = 167). Case report-focused analysis (N = 27) showed five cases of pregnancy PHP-HCa-P and three rep

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021.

The second year of the COVID-19 pandemic had no adverse effect on the number of new drug approvals by the US Food and Drug Administration (FDA). Quite the contrary, with a total of 50 new drugs, 2021 belongs to the most successful FDA years. We assign these new drugs to one of three levels of innovation: (1) first drug against a condition ("first-in-indication"), (2) first drug using a novel molecular mechanism ("first-in-class"), and (3) "next-in-class", i.e., a drug using an already exploited molecular mechanism. We identify 21 first-in-class, 28 next-in-class, and only one first-in-indicati

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… Inhibiting ANGPTL3 preserves lipoprotein lipase and endothelial lipase activities, thus reducing levels of plasma triglyceride and LDL-C (Markham 2021b ). …

Physiological Role and Use of Thyroid Hormone Metabolites - Potential Utility in COVID-19 Patients.

Thyroxine and triiodothyronine (T3) are classical thyroid hormones and with relatively well-understood actions. In contrast, the physiological role of thyroid hormone metabolites, also circulating in the blood, is less well characterized. These molecules, namely, reverse triiodothyronine, 3,5-diiodothyronine, 3-iodothyronamine, tetraiodoacetic acid and triiodoacetic acid, mediate both agonistic (thyromimetic) and antagonistic actions additional to the effects of the classical thyroid hormones. Here, we provide an overview of the main factors influencing thyroid hormone action, and then go on t

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… The activity of lipoprotein lipase in blood samples is increased by heparin and non-esterized fatty acids are generated during sample storage. These acids displace T3 and T4 from their binding proteins and cause artificially high levels of the free hormones. …

Премии победителей и резюме 32nd Ежегодный симпозиум Общества протеинов; Бостон, ОЭТ, июль 9-12, 2018.

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Уникальные диагностические и терапевтические функции порфиринов и фтальокянинов в области фотодинамической терапии, визуализации и термостимы.

Порфиринические молекулы играют уникальную тераностическую роль в лечении болезней; они используются для отображения, обнаружения и лечения различных форм заболевших тканей, в том числе в связи с возрастной маркулярной дегенерацией и рядом различных видов рака. В настоящее время основное внимание уделяется клинической съемке опухолей; целенаправленной доставке фотосенитеров и потенциалу фотоэнцедентов в мультимодальных биомедицинских наноплатформах. В настоящем Обзоре подчеркиваются роли порфириновых молекул в области съемки и пдта, а также исследования по совершенствованию их селективного пог

2020 ACVIM Forum On Demand Research Abstract Program.

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Obesity and Cancer: A Current Overview of Epidemiology, Pathogenesis, Outcomes, and Management.

BackgroundObesity or excess body fat is a major global health challenge that has not only been associated with diabetes mellitus and cardiovascular disease but is also a major risk factor for the development of and mortality related to a subgroup of cancer. This review focuses on epidemiology, the relationship between obesity and the risk associated with the development and recurrence of cancer and the management of obesity.MethodsA literature search using PubMed and Google Scholar was performed and the keywords 'obesity' and cancer' were used. The search was limited to research papers publish