Search Results (19,344)

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality, despite advances in pharmacological prevention and treatment. The burden of CVD necessitates implementing the treatment of risk factors including dyslipidemia. Pharmaceutical advancements and in depth understanding of pathophysiology have enabled innovative therapies targeting pathways underlying lipoprotein metabolism disorders. Angiopoietin protein-like 3 (ANGPTL3) plays a crucial role in the regulation of lipoprotein metabolism, therefore being a potential therapeutic target. Inhibition of ANGPTL3 has emerged as a new therapeutic strategy to reduce LDL-cholesterol levels independent of the LDL receptor function. Therapeutic approaches for ANGPTL3 inhibition range from monoclonal antibodies to nucleic acid therapeutics including antisense oligonucleotides and small interfering RNAs. In this review, we briefly explain the structure and mechanism of action of ANGPTL3 and discuss the therapeutic approaches for targeting ANGPTL3 in the clinical setting. We also discuss Evinacumab, a monoclonal antibody, its structure, mechanism of action, safety, tolerability, pharmacokinetics, and pharmacodynamics, as well as its clinical trial-derived results. The antisense oligonucleotides modify ANGPTL3 mRNA to inhibit protein production, and small interfering RNAs induce mRNA degradation; results from clinical trials were reviewed in detail. Finally, we discuss promising gene editing approaches including clustered regularly interspaced short palindromic repeats (CRISPR)/Cas systems. Full article

The synthesis, in particular the industrial production, of pharmaceuticals requires a broad arsenal of synthetic reactions capable of selectively forming specific structural motifs and assembling smaller building blocks into complex molecules. The Chan–Evans–Lam cross-coupling reaction, which forms a bond between a N-nucleophile and an aryl group from a boronic acid, catalysed by copper salts, is a typical example of this synthetic route. Considering the toxicity of copper and the stringent regulatory limits for its residues in final pharmaceutical products, a heterogeneous catalytic approach offers a viable alternative for this transformation. In this work, we present a simply and reproducibly synthesized catalyst based on copper nanoparticles supported on reduced graphene oxide (Cu-rGO), with high efficiency in a model Chan–Lam reaction involving benzimidazole and aniline derivatives with substituted boronic acids. Full article

Lignans are naturally occurring compounds found in a wide variety of plant species, including flaxseed, soybean, pumpkin seed, broccoli, sesame seed, and some berries. Lignans have been used for centuries in both food and traditional herbal medicine. Recently, numerous new lignans and lignan derivatives with diverse biological properties have been identified. Lignans are considered promising for human health due to their hydrogen-donating antioxidant activity together with their ability to complex divalent transition metal cations. They have demonstrated beneficial effects for cardiovascular disease, as well as in maintaining blood glucose levels, supporting cardiac health, promoting anti-obesity effects, decreasing the risk of renal diseases, enhancing brain function, improving skin and gut health, among others. This review explores the biosynthesis and biological effects of lignans, with a particular focus on their antihypertensive and anti-obesity properties, as well as the molecular mechanisms involved. It also highlights recent advances in sustainable lignan extraction techniques that are suitable for human use. The mechanisms underlying these bioactivities are thought to involve hormonal metabolism and availability, antioxidant action, modulation of angiogenesis, and more. However, further research is needed to fully elucidate the molecular pathways through which lignans exert their therapeutic effects. Overall, lignans from various plant sources hold significant potential for application in functional foods, dietary supplements, and pharmaceutical products aimed at preventing and managing a range of health conditions, including hypertension and obesity. Full article

Cyclodextrins (CyDs) are cyclic oligosaccharides that form inclusion complexes that allow organic compounds and other substances to be incorporated into their cavities. Hydroxypropyl-β-cyclodextrin (HP-β-CyD) is frequently used to improve the formulation properties of poorly water-soluble drugs because of its aqueous solubility and biocompatibility. Previous studies have demonstrated that the solubility and biocompatibility of poorly water-soluble anti-cancer agents can be improved by complexation with HP-β-CyD, which in some cases enhances their anticancer activity relative to the unmodified drugs. Advances in formulation strategies have enabled more efficient intracellular delivery, improved tissue and cell selectivity, and controlled release. HP-β-CyD has also been investigated as an active pharmaceutical ingredient, with demonstrated efficiency in treating leukemia and breast cancer. For example, folate-conjugated HP-β-CyD exhibits high selectivity for folate receptor-expressing cells and more potent anti-cancer activity than unmodified HP-β-CyD. Autophagy has been suggested to be involved in this mechanism. The continued development of drug-delivery systems that integrate advanced technologies and materials based on HP-β-CyD holds promise for further advances in cancer therapy. These findings indicate a paradigm shift in the role of HP-β-CyD from a formulation additive to an active pharmaceutical ingredient, suggesting broader applications for HP-β-CyD in anticancer treatments. Full article

The study investigates the presence of emerging contaminants in a river within a watershed located in the Brazilian semiarid region, specifically within the Caatinga biome, emphasizing the importance of environmental monitoring in areas that have historically been underrepresented in scientific research. The analysis focused on the associations between microplastics and pharmaceutical compounds, demonstrating that the discharge of untreated domestic effluents and the low efficiency of sanitation systems increase water resource contamination and threaten water security. The interdependence between these variables underscores the need for integrated public policies for waste management, complemented by environmental education strategies and technological innovations. The work makes an unprecedented contribution to expanding knowledge about emerging pollutants in semiarid environments, highlighting the urgency of holistic approaches, continuous monitoring, and strengthening environmental governance to ensure the sustainability and resilience of ecosystems like the Caatinga in the face of the challenges posed by global environmental change, urban growth, and those outlined in the Sustainable Development Goals. Full article

Brown seaweeds are marine bioresources rich in bioactive compounds such as carbohydrates, proteins, pigments, fatty acids, polyphenols, vitamins, and minerals. Among these substances, brown algae-derived polysaccharides (alginate, fucoidan, and laminarin) have promising industrial prospects owing to their distinctive structural features and diverse biological activities. Consequently, processing technologies have advanced substantially to address industrial requirements for biopolymer quality, cost-effectiveness, and sustainability. Over the years, significant progress has been made in developing various advanced methods for the sake of extracting, purifying, and structurally characterizing polysaccharides. Aside from that, numerous studies reported their broad spectrum of biological activities, such as antioxidant, anti-inflammatory, anticoagulant, and antimicrobial properties. Furthermore, these substances have various industrial, pharmaceutical, bioenergy, food, and other biotechnology applications. The present review systematically outlines the brown algae-derived polysaccharides treatment process, covering the entire value chain from seaweed harvesting to advanced extraction methods, while highlighting their biological activities and industrial potential as well. Full article

Ergot alkaloids derived from lysergic acid have impacted humankind significantly as toxins in agriculture and as the foundations of several pharmaceuticals. Few fungi capable of producing lysergic acid derivatives have been found outside the family Clavicipitaceae. Based on its phylogenetic placement, we hypothesized the recently described fungus Aspergillus aspearensis (Aspergillaceae) would synthesize lysergic acid amides. Cultures of A. aspearensis produced abundant lysergic acid α-hydroxyethylamide (LAH) and lesser amounts of other lysergic acid derivatives. Conidia contained high concentrations of ergot alkaloids, whereas sclerotia contained significantly less. Approximately half of the ergot alkaloids produced were secreted into the culture medium. When spores of A. aspearensis were injected into larvae of the model insect Galleria mellonella, larvae died at a significantly faster rate than control larvae. The fungus produced ergot alkaloids during insect pathogenesis and later produced conidia and sclerotia on cadavers, indicating it can complete its life cycle in an insect. The genome of A. aspearensis contained two complete ergot alkaloid synthesis gene clusters, similar to those of A. leporis; however, unlike its sister species, none of the ergot cluster genes were pseudogenized. Aspergillus aspearensis is a newly discovered source of ergot alkaloids and may be useful for studying and producing these important chemicals. Full article

Background: Libya, a conflict-affected North African country, has a fragile health system and poor surveillance, leaving it largely underrepresented in global estimates. Earlier Libyan reviews were descriptive, lacking breakpoint standardization, isolate-level pooling, or AMR-attributable mortality and DALY estimates. To our knowledge, this study represents the first comprehensive report that integrates phenotypic and genotypic data to estimate deaths and DALYs attributable to AMR-induced mortality and morbidity, describe spatiotemporal patterns, and model future trajectories. Methods: We performed a meta-analysis according to the PRISMA 2020 guideline of Libyan studies reporting phenotypic or genotypic resistance among clinical bacterial isolates (1970–2024), combined with microbiology records from hospitals and national surveillance systems (preregistered in PROSPERO ID: CRD420251066018). Susceptibility results were standardized to CLSI/EUCAST and deduplicated using WHO GLASS first-isolate rules. We used random-effects meta-regression to estimate pooled resistance, and the counterfactual approach of Global Burden of Disease (GBD) was applied to estimate AMR-attributable DALYs. Molecular data on resistance genes, sequence types, and tuberculosis mutations were systematically collected. Results: We included 62 eligible studies together with national and facility-level surveillance datasets, providing isolate-level susceptibility data for 31,439 clinical isolates from Libya. In 2024, we estimated 2183 deaths (95% UI 1752–2614) attributable to AMR, representing 9.7% (95% UI 7.8–11.6) of total deaths with a mortality rate of 15.2 per 100,000 (12.2–18.2). DALYs attributable to AMR increased from 14,628 (95% UI 11,702–17,554) in 1970 to 96,715 (95% UI 77,372–116,058). The highest pooled resistance involved carbapenem-resistant/MDR A. baumannii, third-generation cephalosporin- and fluoroquinolone-resistant Enterobacterales, and carbapenem-resistant P. aeruginosa. Molecular data showed widespread ESBLs, OXA-/NDM-type carbapenemases, plasmid-mediated colistin resistance, high-risk E. coli ST131 and K. pneumoniae ST147 lineages, and canonical drug-resistant M. tuberculosis mutations. Conclusions: Combined with global and regional evidence, our findings suggest a high and increasing burden of AMR in Libya. These findings emphasize the need for rapid expansion of data collection systems, GLASS-aligned surveillance, diagnostic capacities, and infection control measures. Full article

Background/Objectives: Essential oils (EOs) from plants of the genus Cinnamomum have been widely used based on their antimicrobial, antioxidant, and anti-inflammatory properties. However, their elevated volatility and limited aqueous solubility restrict their use in pharmaceutical and food formulations. Cyclodextrins (CDs) have emerged as a promising strategy to overcome these limitations through the formation of inclusion complexes. Methods: In this study, inclusion complexes of essential oil from C. camphora L. (EOCNM) with β-cyclodextrin (β-CD) were developed using physical mixing (PM), ultrasonic treatment (US), and freeze-drying (FD). The inclusion complexes were physicochemically characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TG/DTG), X-ray diffraction (XRD), and scanning electron microscopy (SEM) to evaluate their physicochemical interactions and complexation efficiency. Results: Our results demonstrated successful complex formation, with the FD and US methods showing greater amorphization and stronger inclusion characteristics compared to the PM method. Thermal analysis confirmed improved physicochemical stability of the essential oil when complexed with β-CD. Furthermore, the cytotoxicity assay of the complexes was assessed using the MTT assay and J774 macrophage cells. The complexes exhibited low cytotoxicity, indicating their potential biocompatibility for biomedical and food applications. Conclusions: Overall, β-CD encapsulation effectively enhanced the physicochemical stability and safety profile of C. camphora essential oil, providing a promising strategy for its controlled delivery and protection against degradation. Full article

Background/Objectives: One-dose packaging is beneficial for older adults and those on multiple medications because it ensures that no doses are missed and supports medication adherence. However, conventional one-dose packaging materials have high moisture permeability, making them unsuitable for the storage of hygroscopic medications. We evaluated the barrier performance of food packaging materials against moisture and oxygen and investigated their potential to enhance the physical stability of the highly hygroscopic sodium valproate, under stressed storage conditions. Methods: Barrier performance was evaluated by measuring the water vapor transmission (WVTR) and oxygen transmission rates of each packaging material. Then, we evaluated the stability of sodium valproate tablets in different food packaging films by measuring weight change, breaking force, and visual appearance over 14 days under stressed storage conditions (35 °C and 75% relative humidity). Conventional cellophane-laminated polyethylene was used as the reference. Results: The WVTR of the food packaging films were below 2 g/m²/day, less than that of the conventional material. Tablets stored in Materials A and B showed weight increases of no more than 1.2% after 3 days, whereas the maximum increase among all food films was 3.7% (Material C). For Materials A and B, the breaking force remained measurable and the visual appearance unchanged throughout the 14-day period, whereas Material C became unmeasurable by day 14. Tablets packaged in cellophane-laminated polyethylene exhibited deliquescence, with visible deformation and stickiness within 3 days, rendering them unmeasurable. Conclusions: Food packaging materials with high barrier performance offer a practical, safe, and effective solution for one-dose packaging of hygroscopic medications, potentially expanding their clinical use and improving adherence. Full article

The post-implantation phase of mammalian development is crucial yet challenging to study due to ethical and technical constraints, particularly in humans. Recent revolutionary advances in extended in vitro culture systems for mammalian embryos now offer unprecedented windows into this developmental “black box”. This review synthesizes how these platforms, alongside stem cell-derived embryo models, are transforming our ability to model early human development in a dish. We detail the technological evolution from two-dimensional (2D) to three-dimensional (3D) cultures that support mouse, non-human primate, and human embryos through key stages of implantation and gastrulation, recapitulating events like lineage specification and axial patterning. Furthermore, we explore how these models serve as powerful tools for investigating the etiology of early pregnancy failure, screening for developmental toxicity of pharmaceuticals, and deciphering the molecular pathogenesis of birth defects. By bridging fundamental embryology with clinical and pharmacological applications, these innovative models herald a new era in biomedical research, holding significant promise for advancing reproductive medicine and regenerative strategies. Full article

This study includes a comparative analysis of four graphene-based electrochemical sensors used for the detection of melatonin, an endogenous hormone involved in circadian rhythm regulation and associated with various neurological pathologies. The sensors were based on screen-printed electrodes (SPE) modified with graphene (G), graphene modified with gold nanoparticles (AuNPs/G), graphene oxide (GO), and reduced graphene oxide (rGO). Melatonin was extracted from commercially available pharmaceutical products, purified, and characterized using UV-Vis spectroscopy, FTIR spectrometry, and HPLC. The performance of the electrodes was evaluated via cyclic voltammetry, using potassium ferrocyanide and standard melatonin solutions to determine the kinetic characteristics, while square-wave voltammetry was employed to determine the detection and quantification limits. G/SPE showed the best performance, with a detection limit of 0.3424 μM, followed by AuNPs/G/SPE with an LOD of 1.2768 μM. GO/SPE had the poorest performance (LOD 23.1056 μM), and rGO/SPE had an LOD of 5.8503 μM. Testing of sensors on pharmaceuticals showed accurate quantification of melatonin in a complex environment. The results highlight the potential of G/SPE and AuNPs/G/SPE sensors for use in the rapid and accurate detection of melatonin in pharmaceutical and biomedical applications. Full article

In recent years, sialidases (neuraminidases) derived from non-clinical sources have attracted considerable interest due to their potential applications in the food and pharmaceutical industries. A deeper understanding of the mechanisms regulating sialidase synthesis could lead to more efficient enzyme production. Induction is considered a key regulatory mechanism. However, there is a lack of data on the regulation of sialidase synthesis in filamentous fungi. This study examines how regulatory mechanisms influence the production of a sialidase enzyme exhibiting high activity at low temperatures in the Antarctic fungal strain Penicillium griseofulvum P29. The inclusion of high- and low-molecular-weight substances possessing terminal non-reducing N-acetylneuramyl groups in the tests led to a marked enhancement of sialidase activity. The strongest induction response was elicited by sialic acid, followed by glycomacropeptide, milk whey, N-acetylglucosamine, N-acetylmannosamine, and colominic acid. RT-qPCR experiments demonstrated that induction occurs at the transcriptional level of the sialidase gene. Biochemical analysis elucidates the function of inducers as triggers in the de novo synthesis of the enzyme protein. To our knowledge, this is the first study to highlight the importance of regulatory mechanism induction in the synthesis of cold-active sialidases. Full article

Background/Objectives: Retinitis pigmentosa is a degenerative retinal disease and a major cause of inherited blindness globally. The pro-survival kinase AKT is downregulated in degenerating photoreceptors in retinitis pigmentosa, and its activation has shown neuroprotective effects in retinitis pigmentosa and other neurodegenerative disorders. In this study, we evaluated the therapeutic potential of SC79, a pharmaceutical AKT activator, in two mouse models of retinitis pigmentosa, rd1.GFP and RhoP23H.GFP. Methods: SC79 was administered intravitreally at postnatal day 12 (P12) and analysis was conducted at P16. Results: SC79 at 10 µM was well tolerated in wildtype mice, with no reduction in retinal function or thickness. In rd1.GFP mice, SC79 partially preserved peripheral outer nuclear layer (ONL) thickness, improved rod photoreceptor-driven optomotor contrast sensitivity responses, and improved cone photoreceptor morphology. Immunohistochemistry of retinal sections indicated AKT-related protein expression changes in both sham and SC79-treated rd1.GFP retinas, with sham injections leading to decreases in this pathway and SC79 injections restoring this back to uninjected protein levels or higher, indicating the damage from intravitreal injections can induce AKT-related protein expression changes. In RhoP23H.GFP mice, changes to the visual response from the therapeutic effects of SC79 were not detectable. An increased dosage of SC79 at 100 µM was evaluated in wildtype mice and showed no major toxic effects, although it did not confer neuroprotective benefits in either disease model. Conclusions: These results demonstrate the potential therapeutic effect of AKT pathway modulation for preserving photoreceptors in recessive retinitis pigmentosa, with further optimisation of treatment delivery required. Full article

Epigenetics involves heritable changes in gene expression—such as DNA methylation (5-methylcytosine; 5mC), histone modifications, and regulation by non-coding RNAs at the mRNA translation level—without altering the underlying DNA sequence. As targeting these mechanisms enables intervention at the root cause of disease rather than the symptoms alone, epigenetics has become a rapidly advancing field in pharmaceutical sciences. Various epigenetic modulators, including histone deacetylase (HDAC) inhibitors, histone acetyltransferase (HAT) inhibitors, DNA methyltransferase (DNMT) inhibitors, and microRNAs (miRNAs), have been developed, and some have already been approved for cancer therapy. However, these agents often face significant challenges such as poor membrane permeability, enzymatic instability, and suboptimal biodistribution. Incorporating functionalized accessory units—serving as vectors (e.g., transporter recognition units, cell-penetrating peptides, tumor-homing peptides, monoclonal antibodies) or as carriers (e.g., monoclonal antibodies, nanoparticles)—into epigenetic modulators may help overcome these delivery barriers. In this narrative review, I discuss the potential and advantages of effective non-invasive delivery of epigenetic drugs using such functionalized accessory unit conjugates. Full article