Search Results (10,989)

Strongyloidosis is a parasitic disease caused by Strongyloides stercoralis, a nematode with a complex life cycle that facilitates long-term persistence within the host. The infection affects millions of people in tropical and subtropical regions and poses a particular challenge in immunocompromised individuals. Although conventional treatments, such as ivermectin and albendazole, are generally effective, emerging concerns regarding drug resistance and adverse effects have prompted the search for alternative therapeutic options. In this context, natural products—including plant extracts, bioactive phytochemicals, and nanoparticle-based formulations derived from natural sources—are emerging as promising anti-Strongyloides potential. This review summarizes recent studies on natural products with anthelmintic activity against strongyloidiasis, with emphasis on their mechanisms of action, efficacy, and future perspectives. A systematic search of the literature was conducted using terms related to Strongyloides, plant species, extracts, and bioactive compounds with nematocidal activity. Eligible studies included those reporting the activity of plants, plant extracts, and their purified metabolites against Strongyloides spp. Data were compiled into a comprehensive table including year of publication, author, plant species, active principle, application conditions, and target nematode species. The pharmacological treatment of this parasite varies according to its life cycle stage. Various biomolecules, phytoactive compounds, and novel plant-based formulations have demonstrated promising activity and may be considered both for treatment and for inclusion in control programs for strongyloidiasis. This review highlights medicinal plants and phytochemicals with ethnopharmacological background and experimentally validated activity against Strongyloides spp., integrating evidence from in vitro, in vivo, and experimental models, as well as clinical trials. Full article

Background/Objectives: Drug products on the pharmaceutical market must meet a number of requirements that guarantee their quality, safety, and efficacy. Accordingly, periodic inspection of the content of active pharmaceutical ingredients (APIs) in marketed drug products is carried out, confirming that they meet all quality and quantity requirements for a given drug formulation before the expiration date. Therefore, the purpose of this study was to evaluate the suitability of the most commonly used thermal analysis methods, differential thermal analysis (DTA), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA), in the control of the composition of commercially available drug products. Results: Based on a review of the literature, it was shown that thermal methods can be useful in distinguishing drug products from different manufacturers, which guarantees their usefulness in quality control of finished drug products and detecting drug products from illegal manufacturers. They are also useful as tools for confirming the presence of APIs in dosage forms under investigation. The cited literature also indicates that DSC and TGA methods can be used in the quantification of APIs in marketed drug products and to detect non-compliant drug products. The use of chemometric techniques to interpret thermal data can eliminate the adverse effects of excipients on quantification results. Conclusions: Thermal methods are a good complement to chromatographic and spectroscopic methods, with the particular advantages of not needing any sample pretreatment, low sample weight, and short analysis time. Full article

Petrochemicals currently represent the predominant global source of energy and consumer products, including the starting materials used in the platform chemical, plastic polymer, and pharmaceutical industries. However, in recent years, the world’s approaches have shifted towards green chemistry and bio-based chemical production in an effort to reduce CO₂ emissions and mitigate climate change. Over the past few decades, researchers have discovered that marine metabolites, primarily sourced from invertebrates, can be utilized to create sustainable and renewable chemicals. This review highlights the significance of advancing marine microorganism-based biotechnology and biochemistry in developing effective conversion systems to enhance the biological production of key platform chemicals, including those utilized as biomaterials and for energy. A background in marine metabolite biochemistry lays the groundwork for potential strategies to mitigate dependence on petroleum for consumer products. This is followed by a discussion of petroleum product replacement technologies, green chemistry alternatives, and CO₂ mitigation efforts for the production of sustainable and renewable key platform chemicals. Full article

Background/Objectives: Therapeutic strategies for Neurofibromatosis Type I (NF1) that correct the underlying pathogenic NF1 variant hold promise for restoring neurofibromin function, reducing tumor burden, and improving patient outcomes by addressing the root cause of the disease rather than its symptoms. Beyond gene editing, transcript reprogramming via RNA trans-splicing has gained attention, particularly with the recent FDA approval of two trans-splicing-based drugs for IND phase 1/2a trials. This study tests whether trans-splicing group I intron ribozymes from Tetrahymena thermophila can be used to repair pathogenic variants of NF1 (pre-)mRNA by 3′-tail replacement. Methods: Splice sites on the NF1 mRNA were identified computationally and validated biochemically, and an efficiency-enhancing Extended Guide Sequence (EGS) of the corresponding ribozyme was identified in a combinatorial experiment. Results: The correct trans-splicing product of this ribozyme was validated in HEK293 NF1−/− cells expressing mNf1. Conclusions: This study established a splice site and activity-enhancing extended guide sequences for the repair of NF1 mRNA. Further optimization of the ribozyme, as well as improved delivery methods, may establish ribozyme-based RNA repair as a viable strategy for NF1 treatment. Full article

Herpesviruses are prevalent infectious agents in humans, with complex structures and life cycles. The viability and detail of a model of capsid assembly and maturation can now be examined against the recently available mature herpesvirus capsids structures. The first large assembly product is the icosahedral procapsid with an outer shell composed of major capsid proteins (MCPs) connected by triplexes (heterotrimers composed of one Tri1 protein and two Tri2 proteins), and an inner shell of scaffold proteins. The asymmetric triplexes have specific and conserved orientations, suggesting a key role in assembly. In the mature capsid structures, triplexes bound to three MCPs may represent an assembly unit where, in most cases, the N-terminus of one MCP wraps around the E-loop of another MCP. The model accommodates the incorporation of a portal into capsid, required for genome encapsidation and viral viability. Cleavage of the scaffold triggers maturation of procapsid. Each of the MCPs rotates mostly as a rigid body, except for the flexible peripheral parts that remodel to close the capsid inner surface. Angularization of the capsid shifts the portal outward to a better contact with the capsid shell. Understanding these events in the herpesvirus life cycle to atomic detail could facilitate the development of drugs that uniquely target assembly and maturation. Full article

Triple-negative breast cancer (TNBC) urgently requires new therapeutic strategies due to the limited efficacy of conventional treatments. Recently, PANoptosis, an integrated form of apoptosis, necroptosis, and pyroptosis, has emerged as a promising target in cancer therapy, though effective agents remain scarce. Paclitaxel, a Taxus-derived natural product, is often combined with other drugs to enhance efficacy, yet optimal combinations are limited. This study investigates the synergistic antitumor effects of paclitaxel and cephalomannine in TNBC, focusing on oxygen-regulated cell death pathways. Network pharmacology and molecular docking revealed that the combination targets multiple cell death- and inflammation-related proteins, including BCL2L1, MAPK14, SYK, TNF, and ADAM17, suggesting multi-target synergy. In vitro, the combination significantly inhibited MDA-MB-231 cell viability, proliferation, and migration, while inducing apoptosis and necrosis. Mechanistically, co-treatment markedly increased intracellular ROS levels and γ-H2AX expression, indicating oxidative stress and DNA damage, both of which were reversible by ROS inhibition. Further analysis demonstrated that the treatment activated the p38 and p53 pathways, regulated the Bax/Bcl-2 ratio, and initiated mitochondrial apoptosis. It also promoted RIPK1/RIPK3/MLKL phosphorylation and MLKL membrane translocation, triggering necroptosis, as well as upregulated NLRP3, cleaved Caspase-1, and GSDMD, inducing pyroptosis. The use of specific inhibitors partially reversed these effects, confirming the involvement of ROS-mediated PANoptosis. Similar antitumor effects were also observed in BT-549 cells, indicating the broad applicability of this combination in TNBC. MCF-10A cells exhibited mild but acceptable cytotoxicity, reflecting manageable side effects typical of chemotherapeutic agents. In vivo experiments further validated the combination’s antitumor efficacy and safety. In summary, paclitaxel and cephalomannine synergistically induce PANoptosis in TNBC through oxygen-regulated cell death pathways, offering a novel therapeutic strategy based on oxidative stress modulation by natural compounds. Full article

Background: Enhancing bioavailability is the target of most pharmaceutical research; this can be achieved by modifying the physico-chemical characteristics of poorly water-soluble drugs intended for oral administration using different techniques. The preparation of liquitablets by blister molding technique provides an opportunity to increase the bioavailability of the drug using an optimal combination of release-facilitating additives. Lornoxicam is an effective non-steroidal anti-inflammatory drug with low water solubility. This study aimed to formulate a novel lornoxicam-containing liquitablets. The effect of different drying techniques on the physico-chemical properties and in vitro dissolution of lornoxicam was investigated. The physical parameters of the tablets were also studied. Methods: The additives applied in the formulation included Tween^® 80, Polyvinylpyrrolidone (PVP K90), Avicel^® PH-102, and sodium bicarbonate. Vacuum-drying and freeze-drying were employed to produce liquitablets. The influence of various drying methods on crystallinity and intra- and interparticle phenomena was investigated. In Vitro dissolution tests were performed at pH 1.2, and a comparison was made between our products and commercial tablets using the pairwise similarity factor model (f2). Results: The liquitablets demonstrated high hydrophilicity and a lower crystallinity of the drug. Freeze-dried liquitablet showed improved dissolution compared to that of the pure drug or the vacuum-dried product. A similarity was observed between our freeze-dried product and the marketed fast-release tablets. Conclusions: This research demonstrates that preparation of liquitablet in combination with freeze-drying has a significantly positive effect in improving the in vitro dissolution rate of lornoxicam. Full article

Lung cancer is the leading cause of cancer mortality worldwide, with a poor prognosis driven by late diagnosis, systemic toxicity of existing therapies, and rapid development of multidrug resistance (MDR) to agents such as paclitaxel and cisplatin. MDR arises through multiple mechanisms, including overexpression of efflux transporters, alterations in apoptotic pathways, and tumour microenvironment-mediated resistance. The application of nanotechnology offers a potential solution to the aforementioned challenges by facilitating the enhancement of drug solubility, stability, bioavailability, and tumour-specific delivery. Additionally, it facilitates the co-loading of agents, thereby enabling the attainment of synergistic effects. Halloysite nanotubes (HNTs) are naturally occurring aluminosilicate nanocarriers with unique dual-surface chemistry, allowing hydrophobic drug encapsulation in the positively charged lumen and functionalisation of the negatively charged outer surface with targeting ligands or MDR modulators. This architecture supports dual-delivery strategies, enabling simultaneous administration of phytocannabinoids and chemotherapeutics or efflux pump inhibitors to enhance intracellular retention and cytotoxicity in resistant tumour cells. HNTs offer additional advantages over conventional nanocarriers, including mechanical and chemical stability and low production cost. Phytocannabinoids such as cannabidiol (CBD) and cannabigerol (CBG) show multitarget anticancer activity in lung cancer models, including apoptosis induction, proliferation inhibition, and oxidative stress modulation. However, poor solubility, instability, and extensive first-pass metabolism have limited their clinical use. Encapsulation in HNTs can overcome these barriers, protect against degradation, and enable controlled, tumour-targeted release. This review examined the therapeutic potential of HNT-based phytocannabinoid delivery systems in the treatment of lung cancer, with an emphasis on improving therapeutic selectivity, which represents a promising direction for more effective and patient-friendly treatments for lung cancer. Full article

Background/Objectives: Recent advancements in innovative drug delivery nanosystems have significantly impacted wound healing, particularly through the incorporation of natural products. This study aimed to develop and characterize a Phlomis crinita extract-loaded nanostructured formulation (PCE-NF) as a topical therapy for skin wounds. Methods: This study involved the incorporation of P. crinita extract in a nanoemulsion by the high-energy emulsification method. This formulation was subjected to physicochemical and biopharmaceutical characterization, and a physical stability study over 30 days. Biocompatibility, tolerability, and irritant effects were assessed, while the wound healing potential was evaluated using in vitro skin models of fibroblasts and keratinocytes. Results: PCE-NF showed a homogeneous appearance with nanometric-sized spherical droplets of 212.27 nm and Newtonian behavior. This formulation showed a sustained release of its majority component (luteonin 7-(6″-acetylglucoside)), which followed a hyperbolic kinetic while showing high permeation, through healthy human skin, with 22.01 µg after 27 h. There were no cytotoxic effects of PCE-NF with improvements in skin barrier function and hydration levels. The wound healing potential of PCE-NF at 3.125 µg/mL was evidenced by enhanced cell migration and accelerated wound closure in 3T3-L1 and HaCaT cells, with values of 94.24 and 92.41%, respectively. Conclusions: These results suggest that this formulation could be used as an effective wound healing treatment. Full article

Increased drug metabolism and elimination are prominent mechanisms mediating multidrug resistance (MDR) to not only chemotherapy drugs but also anti-cancer natural products, such as benzyl isothiocyanate (BITC). To evaluate the possibility of combined utilization of a certain compound to overcome this resistance, we focused on glutathione S-transferase (GST)-dependent metabolism of BITC. The pharmacological treatment of a pi-class GST-selective inhibitor, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX), significantly increased BITC-induced toxicity in human colorectal cancer HCT-116 cells. However, NBDHEX unexpectedly increased the level of the BITC–glutathione (GSH) conjugate as well as BITC-modified proteins, suggesting that NBDHEX might increase BITC-modified protein accumulation by inhibiting BITC–GSH excretion instead of inhibiting GST. Furthermore, NBDHEX significantly potentiated BITC-induced apoptosis with the enhanced activation of apoptosis-related pathways, such as c-Jun N-terminal kinase and caspase-3 pathways. These results suggested that combination treatment with NBDHEX may be an effective way to overcome MDR with drug efflux and thus induce the biological activity of BITC at lower doses. Full article

Lung cancer remains a foremost cause of cancer-related impermanence globally, demanding innovative and effective therapeutic strategies. Polymeric nanoparticles (NPs) have turned up as a promising transport system for drugs due to their biodegradability, biocompatibility, and capability to provide controlled and targeted release of therapeutic agents. This review offers a thorough examination of different polymeric NP platforms, such as chitosan, gelatin, alginate, poly (lactic acid), and polycaprolactone, highlighting their mechanisms, formulations, and applications in the treatment of lung cancer. These NPs facilitate the delivery of chemotherapeutic agents, gene therapies, and immune modulators, with enhanced bioavailability and reduced systemic toxicity. Additionally, advanced formulations such as ligand-conjugated, stimuli-responsive, and multifunctional NPs demonstrate improved tumor-specific accumulation and cellular uptake. The review also discusses quantum dots, magnetic and lipid-based NPs, and green-synthesized metallic polymeric hybrids, emphasizing their potential in theranostics and combination therapies. Preclinical studies show promising results, yet clinical translation faces challenges; for example, large-scale production, long-term toxicity, and regulatory hurdles. Overall, polymeric NPs represent a powerful platform for advancing personalized lung cancer therapy, with future prospects rooted in multifunctional, targeted, and patient-specific nanomedicine. Full article

Cellulose nanofibril (CNF)-based hydrogels, owing to their sustainability, biocompatibility, and versatile mechanical properties, are promising for biomedical applications. This review analyzes the recent advances and biomedical applications of CNF hydrogels. CNF hydrogels can be prepared via physical and chemical crosslinking. Physical crosslinking involves surface charge density control, pH manipulation, and flow-based processing to generate stable networks, whereas chemical crosslinking employs agents such as epichlorohydrin and citric acid to form permanent covalent bonds. These approaches enable precise control over hydrogel properties, including mechanical strength, porosity, and stimuli responsiveness. CNF hydrogels are particularly promising in drug delivery systems and tissue engineering. CNFs as drug delivery vehicles offer enhanced bioavailability and drug loading capacity owing to their open pore structure and large surface area. Recent developments in stimuli-responsive and injectable CNF hydrogels have enabled controlled drug release and improved targeting capabilities. Moreover, CNF hydrogels serve as effective scaffolds for cell growth and tissue regeneration, with applications in cartilage engineering and wound healing. Integrating CNF hydrogels with 3D bioprinting technology has generated complex tissue structures. However, several challenges remain, including the need for the standardization of toxicology assessments, optimization of large-scale production processes, and development of sophisticated control mechanisms for drug delivery. Future research should advance manufacturing technologies, improve long-term stability, and develop standardized testing protocols for regulatory compliance. Full article

Background: Gold nanoparticles (AuNPs) have several beneficial properties that make them effective as intracellular drug carriers, and their potential for various diagnostic and therapeutic applications is gaining recognition. Depending on their size and shape, AuNPs can cross the central nervous system (CNS) through the blood–brain barrier (BBB). In the CNS, they can exert a variety of influences on neuronal and glial cells, which can be both supportive—promoting cell health and function—and cytotoxic, potentially leading to cellular damage. The hypothalamus (HT) is the first region where nanoparticles (NPs) interact, as this neuroendocrine center is particularly sensitive to factors in the systemic circulation due to its function and location. This area is affected by systemic factors, including pro-opiomelanocortin (POMC) neurons, which regulate metabolic function and maintain homeostasis. The activity of mitochondria within these cells influences their response to both external factors and the presence of AuNPs, thereby facilitating a complex interplay between nanoparticle interactions and cellular metabolism in this vital brain region. Aims: This study investigates how AuNPs, at different concentrations and exposure times under in vitro conditions, affect the mitochondrial activity of POMC neurons, aiming to provide a comprehensive understanding of the mechanisms in the HT. Methods: The study investigates the effect of varying gold nanoparticle concentrations on the mitochondrial activity of POMC neurons over treatment periods of 1, 15, 24, and 48 h. Mitochondrial activity was measured using a Seahorse XFp Analyzer to provide high-resolution insights. Additionally, mitochondrial functionality was assessed through the detection of reactive oxygen species (ROS) and cell viability. Results: The findings indicated that the effects of gold nanoparticles on mitochondrial activity depend significantly on their concentration and exposure time. Specifically, exposure leads to an increase in early response systems, the citric acid cycle, and proton efflux, ultimately resulting in the inhibition of mitochondrial function and ATP production in POMC cells. This disruption may affect hypothalamic regulation and energy metabolism. Full article

Background: Worldwide, the number of cases of parasitic diseases has been increasing; however, available treatments have variable adverse effects and low efficacy, mainly in Neglected Tropical Diseases such as Chagas disease and Leishmaniasis. Therefore, the development of new and more effective antiparasitic drugs is important. Natural products are the source of secondary metabolites with different biological activities, such as antibacterial, anticancer, anti-inflammatory, and antiparasitic. Objectives: In this work, secondary metabolites (phenols and terpenes) from natural products were selected to be evaluated against the epimastigotes of NINOA and A1 strains of Trypanosoma cruzi and the promastigotes of M379 strain and FCQEPS native isolate of Leishmania mexicana. Additionally, their cytotoxicity and selectivity index were determined. Methods: Eighteen secondary metabolites were evaluated in vitro against T. cruzi epimastigotes and L. mexicana promastigotes; additionally, their cytotoxicity on the J774.2 macrophage cell line was determined. Results: The compounds l-(-)-menthol (14, IC₅₀ = 24.52 µM) and β-citronellol (11, IC₅₀ = 21.54 µM) had higher trypanocidal activity than the reference drug (benznidazole) against NINOA and A1 strains of T. cruzi, respectively. On the other hand, para-anisyl alcohol (4, IC₅₀ = 34.89 µM) had higher leishmanicidal activity than the reference drug (glucantime^®) against M379 and the FCQEPS native isolate of L. mexicana. Finally, in silico, the determination of their pharmacokinetic and toxicological properties showed that they are promising candidates for oral and topical uses. Conclusions: This study opens the possibility of using secondary metabolites as scaffolds for access to the development of new molecules for the treatment of parasite diseases. Full article

The apoptotic mechanism is complex and involves many pathways. Defects can occur at any time along these pathways, resulting in malignant cell transformation and resistance to anticancer drugs. Collective efforts have made great progress in the implementation of natural products in clinical use and in discovering new therapeutic opportunities. This study aimed to screen volatile compounds of Warburgia salutaris leaf extracts and investigate their pro-apoptotic effects on MCF-7 cells. The approach was mainly based on determining cell viability using MTT and scratch assays, and DNA synthesis and damage using BrdU and comet assays, respectively. DAPI/PI stains were used for morphological analysis and expression was determined by RT-PCR and human apoptotic proteome profiler. Warburgia salutaris extracts exhibited antiproliferative effects on MCF-7 cells in a time- and dose-dependent manner. Acetone and methanol extracts exhibited low IC₅₀ at 24, 48 and 72 h. Furthermore, the scratch test revealed that MCF-7 does not metastasise when treated with IC₅₀. Expression showed upregulation of pro-apoptotic proteins and executioner caspases. Taken together, these findings suggest that leaves can promote apoptosis through the intrinsic apoptotic pathway, as observed by upregulation of the Bax and caspase 3 proteins. This paper provides new insights into the mechanisms of action of W. salutaris leaf extracts in the development of anticancer drugs. Full article