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Molecular Diversity of Lupane Hybrids in Drug Design and Materials Science.

The need for new, more effective drugs to treat cancer, infectious diseases, various parasitic infestations, and metabolic disorders requires innovative approaches to the design of promising molecules. One of these areas is the creation of hybrid structures. Lupane triterpenoids are of significant interest for such research due to their high abundance in natural sources and their renewable nature, their molecular architecture, presence of several easily modifiable functional groups, enantiomeric purity, broad spectrum of biological activity, and low toxicity. Active research into the biologica

Совпадение в полном тексте источника
… Acylation of the 3-OH group in BA, followed by allylic bromination using NBS, produced 3β-acetoxy-30-bromo-lup-20(29)-en-28-oic acid. At a concentration of 100 μM, this compound inhibited the viability of L. amazonensis promastigote forms by 47.41%. …

Imiglucerase in the treatment of Gaucher disease: a history and perspective.

The scientific and therapeutic development of imiglucerase (Cerezyme(®)) by the Genzyme Corporation is a paradigm case for a critical examination of current trends in biotechnology. In this article the authors argue that contemporary interest in treatments for rare diseases by major pharmaceutical companies stems in large part from an exception among rarities: the astonishing commercial success of Cerezyme. The fortunes of the Genzyme Corporation, latterly acquired by global giant Sanofi SA, were founded on the evolution of a blockbuster therapy for a single but, as it turns out, propitious ul

Advanced Technologies for Large Scale Supply of Marine Drugs.

Marine organisms represent a source of unique chemical entities with valuable biomedical potentialities, broad diversity, and complexity. It is essential to ensure a reliable and sustainable supply of marine natural products (MNPs) for their translation into commercial drugs and other valuable products. From a structural point of view and with few exceptions, MNPs of pharmaceutical importance derive from the so-called secondary metabolism of marine organisms. When production strategies rely on marine macroorganisms, harvesting or culturing coupled with extraction procedures frequently remain t

Отличительные стратегии распознавания tRNA, используемые гомологической семьей редактирующих доменов, предотвращают неправильный перевод.

Ошибки в синтезе белка из-за пропускания аминокислот с tRNA ставят под угрозу жизнеспособность клеток. Было описано несколько контрольно-пропускных пунктов для предотвращения образования Ala- и Cys-tRNA(Pro), в том числе специально для Ala редактируемый домен (INS) большинства бактериальных проли-тринских синтезаторов (PRS) и автономный однодомный INS homolog, YbaK, который очищает Cys-tRNA(Pro) в транс. Во многих видах, где у ПРОРС нет домена INS, за редактирование Ala-tRNA(ProXp-ala) отвечает другой однодомный белок, похожий на INS. Хотя аминокислотная специфичность этих доменов редактирован

Совпадение в аннотации оригинала
Errors in protein synthesis due to mispairing of amino acids with tRNAs jeopardize cell viability. Several checkpoints to prevent formation … in substrate selection has not been investigated in detail. Critical recognition elements for aminoacylation by bacterial ProRS include acceptor stem elements G72/A73 and anticodon bases G35/G36. Here, we show that ProXp-ala and INS require these same acceptor stem and anticodon elements, respectively, whereas YbaK lacks inherent tRNA specificity. Thus, th …

Cyclic Peptides in Modern Drug Discovery: Trends and Therapeutic Directions.

Peptide therapeutics are an important drug modality due to their high specificity, favorable safety, and expanding design potential. Among them, cyclic peptides occupy a space between small molecules and biologics, offering improved rigidity, stability, and target engagement. This report analyzes trends in cyclic peptide research using data from the CAS Content Collection over the past two decades. Results show a steady rise in academic publications and patents, reflecting growing interest across discovery and development. Notably, oral administration is gaining attention, indicating progress

Immune Checkpoint Inhibitors and Immunomodulators for Cancer Immunotherapy: Insights Into Resistance and Therapeutic Strategies.

Cancer immunotherapy has redefined cancer treatment. However, the molecular and cellular basis of immune evasion and therapeutic resistance remains incompletely understood. Early immune checkpoint inhibitors have delivered significant clinical benefit, but their efficacy and durability remain limited in many patients. These limitations have driven the exploration of next-generation immune checkpoints and additional regulatory pathways that shape tumor-immune interactions. Recent advances have broadened the immune checkpoint landscape and revealed new targets. These targets operate within inter

The Multifaceted Nature of GLP-1: Molecular Mechanisms and Signaling Pathways in Metabolic and Neurodegenerative Diseases.

The aim of this article is to present the current state of knowledge regarding the use of GLP-1 agonists in the treatment of type 2 diabetes, obesity, and other potential clinical indications, including neurodegenerative conditions. The article describes the characteristics of the diseases discussed, with particular emphasis on the pathophysiological mechanisms and the impact of metabolic disorders on the course of the diseases. In addition, the specific role of GLP-1 receptor agonists and their mechanisms of action leading to improved clinical outcomes were discussed, including their impact o

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… Liraglutide is an acylated derivative of human GLP-1. It is characterized by 97% homology with the native peptide [ 9 ]. … The authors mentioned above confirm that, thanks to structural modifications in the form of acylation or the use of polymer carriers, modern GLP-1 analogs enable a longer-lasting pharmacological effect and less frequent administration of the drug, which increases the effectiveness of treatment and patient …

Exploiting artificial intelligence in precision oncology: an updated comprehensive review.

Precision oncology considers the genetic makeup of both the tumor and the cancer patient, medical history, clinical metadata, lifestyle and environmental factors. Thus, adoption of precision cancer medicine mandates sophisticated integrative analysis. Being a master in sorting and solving the puzzle pieces, artificial intelligence (AI)-powered frameworks emerged to fill the gap via executing multimodal analysis and generating meaningful outputs. Herein, we systematically discussed the opportunities and challenges of exploiting AI-assisted models in preclinical cancer research and in clinical o

An Updated Review on Marine Anticancer Compounds: The Use of Virtual Screening for the Discovery of Small-Molecule Cancer Drugs.

Marine secondary metabolites are a promising source of unexploited drugs that have a wide structural diversity and have shown a variety of biological activities. These compounds are produced in response to the harsh and competitive conditions that occur in the marine environment. Invertebrates are considered to be among the groups with the richest biodiversity. To date, a significant number of marine natural products (MNPs) have been established as antineoplastic drugs. This review gives an overview of MNPs, both in research or clinical stages, from diverse organisms that were reported as bein

Research advances of lactylation modification in breast cancer.

Breast cancer (BC), a leading cause of cancer mortality in women, involves complex molecular mechanisms including post-translational modifications (PTMs). While common PTMs are well-studied, lactylation-a novel PTM linking metabolism to epigenetics-has emerged as a critical regulator in BC pathogenesis. The high concentration of lactate caused by the Warburg effect makes lactylation in tumor tissue possible. Machine learning enhances the discovery and analysis of lactylation sites by processing large datasets, revealing patterns that influence tumor behavior and patient outcomes. This review o

Влияние ПГПР на структуру микробиологической сообщества ризосферы и урожайность солончаковых зерновых культур.

Растворяющиеся в почве бактерии, способствующие росту растений (PGPR), могут защищать растения от почвенных заболеваний и абиотических стрессовых условий. Основная цель данного исследования заключалась в оценке влияния различных PGPR (TF1, TF2, TF3 и TF4) на микробную сообщество ризосферы зерна для корма в солончаково-щелочной поле с использованием высокопроизводительной технологии последовательного секвенирования Illumina MiSeq. Результаты показали, что различные PGPRs значительно увеличили плотность уборки (на 21,31–45,16%), высоту растения (на 9,12–19,98%), диаметр стебля (на 30,07–45,78%)

Адаптация эукариот-подобных PRS к прокариот-подобным tRNAPro.

Синтеты Проли-ТРНА (ПРОРС) уникальны среди аминоачил-тРНК (ААРС) two различные структурные архитектуры различных организмов: прокариота-подобные (П-тип) и эукариоте/археон-подобные (Е-тип). Интересно, что Бакиллус Тюрингьенси гавань обоих типов, сосуществует P-тип (BtProRS1) и E-тип PRS (BtProRS2). Несмотря на свои различия, оба фермента формально выражаются и функционируют в vivo. По аналогии с BtProRS1, BtPRS2 выборочно заряжает TRNAPro типа P и демонстрирует более высокий допуск к галоугинону, чем каноническая PRS. Однако эти two Изозимы признают основные идентификационные элементы типа P t

Dysregulation of sphingolipid metabolism contributes to bortezomib-induced neuropathic pain.

The development of chemotherapy-induced painful peripheral neuropathy is a major dose-limiting side effect of many chemotherapeutics, including bortezomib, but the mechanisms remain poorly understood. We now report that bortezomib causes the dysregulation of de novo sphingolipid metabolism in the spinal cord dorsal horn to increase the levels of sphingosine-1-phosphate (S1P) receptor 1 (S1PR1) ligands, S1P and dihydro-S1P. Accordingly, genetic and pharmacological disruption of S1PR1 with multiple S1PR1 antagonists, including FTY720, blocked and reversed neuropathic pain. Mice with astrocyte-sp

Долгосрочная стабильность и производительность генных движителей на основе Cas9/Guide RNA в анофелиновых комарах.

Разрабатываются стратегии изменения численности населения с целью борьбы с распространением анофелиных комаров паразитов, вызывающих человеческую малярию. Эти подходы направлены на сокращение заболеваемости и заболеваемости за счет распространения доминирующих генов антипаратионного эффекта среди переносчиков инфекции. Для того чтобы штаммы могли оказывать эпидемиологическое воздействие, они должны в течение продолжительного периода времени сохранять свойства привода и подавления паразитов. Three Gene-drive штаммы, AcTP13 и AcTP43 в Anopheles coluszii и AgTP13 в Anopheles gambiae, с автономным

Liposomal Drug Delivery Systems and Anticancer Drugs.

Cancer is a life-threatening disease contributing to ~3.4 million deaths worldwide. There are various causes of cancer, such as smoking, being overweight or obese, intake of processed meat, radiation, family history, stress, environmental factors, and chance. The first-line treatment of cancer is the surgical removal of solid tumours, radiation therapy, and chemotherapy. The systemic administration of the free drug is considered to be the main clinical failure of chemotherapy in cancer treatment, as limited drug concentration reaches the tumour site. Most of the active pharmaceutical ingredien

Pharmacological inhibition of HDAC6 reverses cognitive impairment and tau pathology as a result of cisplatin treatment.

Chemotherapy-induced cognitive impairment (CICI) is a commonly reported neurotoxic side effect of chemotherapy, occurring in up to 75% cancer patients. CICI manifests as decrements in working memory, executive functioning, attention, and processing speed, and greatly interferes with patients' daily performance and quality of life. Currently no treatment for CICI has been approved by the US Food and Drug Administration. We show here that treatment with a brain-penetrating histone deacetylase 6 (HDAC6) inhibitor for two weeks was sufficient to fully reverse cisplatin-induced cognitive impairment

Multidisciplinary Progress in Obesity Research.

Obesity is a chronic disease that endangers human health. In recent years, the phenomenon of obesity has become more and more common, and it has become a global epidemic. Obesity is closely associated with many adverse metabolic changes and diseases, such as insulin resistance, type 2 diabetes mellitus, coronary heart disease, nervous system diseases and some malignant tumors, which have caused a huge burden on the country's medical finance. In most countries of the world, the incidence of cancer caused by obesity is increasing year on year. Diabetes associated with obesity can lead to seconda

Liposomal Doxorubicin in the treatment of breast cancer patients: a review.

Drug delivery systems can provide enhanced efficacy and/or reduced toxicity for anticancer agents. Liposome drug delivery systems are able to modify the pharmacokinetics and biodistribution of cytostatic agents, increasing the concentration of the drug released to neoplastic tissue and reducing the exposure of normal tissue. Anthracyclines are a key drug in the treatment of both metastatic and early breast cancer, but one of their major limitations is cardiotoxicity. One of the strategies designed to minimize this side effect is liposome encapsulation. Liposomal anthracyclines have achieved hi

Metabolic Reprogramming of Cancer Cells and Therapeutics Targeting Cancer Metabolism.

BackgroundCancer metabolism is a field focused on the unique alterations in metabolic pathways that occur in cancer cells, distinguishing them from the metabolic processes in normal cells.MethodsAn extensive review of the current literature on the metabolic adaptation of cancer cells was carried out in the current study.ResultsThe rapidly proliferating cells require high levels of molecules, such as glucose, amino acids, lipids, and nucleotides, along with increased energy demand (ATP). These requirements are met through alterations in the processes involving glucose, amino acid, lipid, and nu

Transformative Impact of Nanocarrier-Mediated Drug Delivery: Overcoming Biological Barriers and Expanding Therapeutic Horizons.

Advancing therapeutic progress is centered on developing drug delivery systems (DDS) that control therapeutic molecule release, ensuring precise targeting and optimal concentrations. Targeted DDS enhances treatment efficacy and minimizes off-target effects, but struggles with drug degradation. Over the last three decades, nanopharmaceuticals have evolved from laboratory concepts into clinical products, highlighting the profound impact of nanotechnology in medicine. Despite advancements, the effective delivery of therapeutics remains challenging because of biological barriers. Nanocarriers offe