Search Results (164)

Patients on standard hemodialysis (HD) show insufficient clearance of medium-molecular-weight uremic toxins, resulting in long-term complications. In this study we investigated the effectiveness of expanded HD (xHD) in the clearance of medium-molecular-weight uremic substances. This prospective study included patients on standard thrice-weekly HD. Participants were treated with xHD for 4 weeks, and the clearance of urea and β2-microglobulin was measured at the beginning and at the end of the study and compared with standard HD (sHD). Moreover, we investigated the clearance of Su-PAR, MCP-1, and activin, comparing sHD, xHD, and online hemodiafiltration (HDF). xHD had the same efficiency in the removal of low-molecular-weight substances compared to sHD but led to a significant decrease in β2-microglobulin levels from the first application of the method (sHD: from 36.9 ± 10.6 to 39.7 ± 18.9 mg/dL, p = 0.595 vs. 1st xHD: from 40 (36.5, 41.8) to 11 (9.8, 13.2) mg/dL, p = 0.008 vs. after 4 weeks on xHD: from 31.5 (28.5, 34.5) to 8.7 (8.2, 9.0) mg/dL, p = 0.008). Moreover, pre-session β2-microglobulin levels significantly decreased after 4 weeks on xHD. Su-PAR, MCP-1, and activin during xHD were also significantly reduced. xHD leads to a significant and cumulative reduction in medium-molecular-weight uremic toxins compared to standard HD. Full article

Adeno-associated virus (AAV) is a promising gene therapy vector due to its high transduction efficiency, low pathogenicity, low immunogenicity, and the ability to mediate the long-term stable expression of exogenous genes. The viral particle titer is an essential quality attribute of recombinant adeno-associated virus (rAAV) gene therapy products. Multiangle light scattering (MALS) is an important means of directly measuring the absolute molecular weight and distribution of macromolecular drugs. This study established and validated a method based on SEC-UV-MALS-RI tandem technology for accurately determining rAAV particle titers. The verification results indicated that the method exhibited good specificity, linearity, precision, accuracy, and durability. Several collaborative laboratories used this method to calibrate the standard substances needed for rAAV particle titer determination. The results suggested that combining the SEC-MALS method with standard substances enables the rapid and accurate measurement of the viral particle titers in rAAV gene therapy products. Full article

The widespread use of polyethylene terephthalate (PET) in bottled water packaging remains significant and is expected to increase further in the coming years. This trend raises concerns due to the generation of large amounts of waste. The degradation of PET leads to the release of low-molecular-weight substances and microplastic particles, which contaminate food products and the environment. This work highlights the significance of microplastic pollution, summarizes the mechanisms of PET degradation, and discusses methods for microplastic detection. A key section of the paper explores potential degradation management strategies, focusing on their applications and existing limitations. The study underscores the need for coordinated action among the scientific community, industry, and policymakers to mitigate this pressing environmental challenge. Full article

Liquid Electron Ionization (LEI) is a powerful and robust interface for the qualitative and quantitative analysis of medium-low-molecular-weight compounds, including numerous environmental pollutants and toxicological substances. Although the robustness and performance of this interface have already been demonstrated, research on its optimization can still improve instrumental performance in terms of detectability. In this study, different setups of the interface’s vaporization micro-channel (VMC) made using different capillaries and various sizes were tested to evaluate the correspondent instrumental performance. The results show that a new combination of capillaries in the interface set up significantly improves instrumental detectability, reaching LOD values almost five times lower than those of the previous setup. Full article

Microplastics (MPs) are ubiquitous in aquatic environments, soils, and beach sediments, demonstrating a remarkable ability to adsorb dissolved organic matter (DOM). Although there are methods for extracting DOM from water, the approaches for directly extracting DOM from microplastics have not been thoroughly investigated, and the characterization of DOM adsorbed on microplastics is also insufficient. In this study, five different types of microplastic samples were collected from each of five environmental media (water and sediment), and finally 25 samples were obtained. This paper comparatively assessed the extraction efficiency of DOM from MPs with various solvents by using total organic carbon (TOC), culminating in the development of a sodium pyrophosphate-NaOH solution extraction method optimized for DOM. The morphology, material and environmental medium of microplastics were the three primary factors affecting the adsorption of DOM on microplastics, with the highest enrichment ratio of 1.4–1.8 times for extruded polyethylene microplastics (EPE-MPs) characterized by their porous structure in the flowing water environment. The molecular weight of DOM adsorbed on microplastics showed a multi-modal distribution pattern with great dissimilarities among the different environmental media. Gel permeation chromatography (GPC) indicated that the weight-average molecular weight (M_w) of DOM was 2750–4552 Da for river MPs, 2760–5402 Da for Qiantang River MPs, 1233–5228 Da for East China Sea MPs, 440–7302 Da for soil sediment MPs and 438–6178 Da for beach sediment MPs, respectively. Excitation-emission matrix-parallel factor analysis (EEM-PARAFAC) identified that tyrosine-like substances with high excitation in region IV and low excitation in region I were predominantly adsorbed on MPs, followed by tryptophan-like substances with low excitation in region II and protein-like substances in region IV, while humic- and fulvic-like substances in regions V and III, respectively, exhibited the least adsorption affinity. The findings underscored the critical need to comprehensively consider the interactions between MPs and DOM and their environmental impacts in pollution control strategies. Full article

Background/Objectives: This review examines the role of pharmacogenomics in individual responses to the pharmacotherapy of various drugs of abuse, including alcohol, cocaine, and opioids, to identify genetic variants that contribute to variability in substance use disorder treatment outcomes. In addition, it explores the pharmacomicrobiomic aspects of substance use, highlighting the impact of the gut microbiome on bioavailability, drug metabolism, pharmacodynamics, and pharmacokinetics. Results: Research on pharmacogenetics has identified several promising genetic variants that may contribute to the individual variability in responses to existing pharmacotherapies for substance addiction. However, the interpretation of these findings remains limited. It is estimated that genetic factors may account for 20–95% of the variability in individual drug responses. Therefore, genetic factors alone cannot fully explain the differences in drug responses, and factors such as gut microbiome diversity may also play a significant role. Drug microbial biotransformation is produced by microbial exoenzymes that convert low molecular weight organic compounds into analogous compounds by oxidation, reduction, hydrolysis, condensation, isomerization, unsaturation, or by the introduction of heteroatoms. Despite significant advances in pharmacomicrobiomics, challenges persist including the lack of standardized methodologies, inter-individual variability, limited understanding of drug biotransformation mechanisms, and the need for large-scale validation studies to develop microbiota-based biomarkers for clinical use. Conclusions: Progress in the pharmacogenomics of substance use disorders has provided biological insights into the pharmacological needs associated with common genetic variants in drug-metabolizing enzymes. The gut microbiome and its metabolites play a pivotal role in various stages of drug addiction including seeking, reward, and biotransformation. Therefore, integrating pharmacogenomics with pharmacomicrobiomics will form a crucial foundation for significant advances in precision and personalized medicine. Full article

Background: Nutraceuticals represent a strategy for maintaining health and constitute a brilliant market in Italy and across Europe. However, the absence of strict regulations regarding formulation requirements highlights a critical issue: their poor bioavailability. An example is coenzyme Q10 (CoQ10), a quinone known for its potential as a mitochondrial protective agent but characterized by low intestinal absorption. CoQ10 is a hydrophobic molecule with high molecular weight and poor water solubility, factors that significantly limit its intestinal bioaccessibility and, consequently, its oral bioavailability. Objectives: In this context, the present study describes a novel formulation designed to enhance CoQ10 bioaccessibility through in situ emulsification upon contact with gastroenteric fluids. This technology, termed Lipid-Based Auto-Emulsifying Drug Delivery System (LiBADDS), is unique because it combines a medium-chain triglyceride (MCT), a long-chain fatty acid, conjugated linoleic acid (CLA) with a high HLB solubilizer, Polysorbate 80 (PS80), and a sodium octenyl succinate starch derivative (SOS), which can create a nanometric emulsion simply by aqueous dispersion and upon contact with gastrointestinal fluids. This phenomenon promotes the prompt dispersion of CoQ10 and its rapid translocation into the serosal compartment of the intestinal epithelium. Methods: Its efficacy was evaluated in vitro through the Caco-2 cellular model and in vivo through a crossover study on healthy volunteers, measuring pharmacokinetic parameters such as AUC, C_max, T_max, ΔAUC, and ΔC_max. Results: Overall, LiBADDS demonstrated a significant improvement in both the bioaccessibility and bioavailability of CoQ10 compared to the unformulated substance. Conclusions: LiBADDS showed to be a promising tool to improve CoQ10 bioavailability by enhancing its bioaccessibility. Full article

Atorvastatin calcium, an antifungal agent, has the potential to be repositioned/repurposed to combat the increasing antimicrobial resistance. However, one of the most crucial issues in developing atorvastatin calcium-loaded products with a topical antifungal effect is achieving the optimal release and dissolution rates of this statin to produce the desired therapeutic effect. In this paper, we report on the development and pharmaceutical assessment of hydrogels composed of low-molecular-weight chitosan, tragacanth, and xanthan gum/pectin/κ-carrageenan as potential drug carriers for atorvastatin calcium for buccal delivery. Multidirectional analysis of the carriers with regard to their drug-release profiles and mucoadhesive, antimicrobial, and cytotoxic properties was accompanied by an evaluation of the freeze-drying process used to improve the hydrogels’ applicability. Using differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy techniques, the role of lyophilization in enhancing atorvastatin calcium delivery from polyelectrolyte complex-based matrices via drug amorphization was demonstrated. The freeze-dried hydrogels had significantly improved release and dissolution rates for the amorphic statin. Therefore, there is great potential for the use of lyophilization in the design of polyelectrolyte complex-based semi-solids in usable dosage forms for numerous crystalline and poorly water-soluble active substances. Full article

The application of oxidation processes, including advanced oxidation, in water treatment is one of the effective methods for eliminating risks associated with the presence of organic substances in water and those formed during chlorination. This article presents the impact of advanced oxidation in the UV + O₃ process on the content and structure of organic substances present in three natural waters with different levels of total organic carbon (TOC). The process was carried out using low-pressure and medium-pressure lamps with an irradiation time of 40 min and ozone doses of 1.5 gO₃/m³ and 5 gO₃/m³. Advanced oxidation, regardless of the type of lamp used or the ozone dose, had the greatest effect on the content of humic acids, which underwent both transformation and mineralization. The use of a low-pressure lamp resulted in an increase in the content of organic substances with the lowest molecular weight (<0.7 kDa), whereas the medium-pressure lamp led to an increase in substances with a molecular weight >1.3 kDa. Regardless of the ozone dose and the type of lamp used, the transformation of organic substances dominated over mineralization, whose efficiency reached a maximum of 44.9% and 38.4% for the low-pressure and medium-pressure lamps, respectively. The degree of organic substance transformation and the efficiency of their removal were directly proportional to the TOC content in the raw water. The use of a low-pressure UV lamp ensured higher process efficiency, which is also associated with lower energy costs. Full article

Astragalus mongholicus, an important medicinal plant species, exhibits low tolerance to high-salt environments, which restricts its growth in saline–alkaline areas. Understanding its salt-tolerance mechanisms is crucial for overcoming the technical challenges of industrialized cultivation in these regions. However, studies on the salt-tolerance mechanisms of Astragalus mongholicus are limited. This study examines two Astragalus mongholicus germplasms with distinct differences in salt tolerance (LQ: salt-tolerant, DT: salt-sensitive), and investigates their physiological adaptations and molecular mechanisms under salt stress (200 mmol/L NaCl) using an integrated analysis of morphology, physiology, metabolomics, and transcriptomics. Specifically, LQ showed smaller reductions in plant height, root length, root thickness, and fresh weight (29.0%, 5.0%, 2.8%, and 22.3%, respectively), compared to DT, which exhibited larger reductions (42.9%, 44.9%, 46.3%, and 41.4%, respectively). The results indicated that the salt-tolerant germplasm (LQ) enhanced antioxidant enzyme activities in response to salt stress, including SOD, POD, and CAT, and accumulating osmoregulatory substances. In LQ, the activities of SOD, POD, and CAT increased by 22.8%, 10.9%, and 8.8%, respectively, significantly higher than those of DT, which showed increases of 2.9%, 8.5%, and 1.4% in SOD, POD, and CAT activities, respectively. The contents of soluble sugar and protein in LQ increased by 2-fold and 16.9%, respectively, compared to 67.0% and 18.8% increases in DT. Additionally, the levels of MDA, H₂O₂, and OFR in LQ showed smaller increases (14.7%, 41.0%, and 13.6%, respectively), compared to the larger increases observed in DT (58.0%, 51.2%, and 18.6%), indicating a reduced level of oxidative damage in LQ and enhanced tolerance to salt stress. Combined transcriptomic and metabolomic analyses revealed that 3510 differentially expressed genes (DEGs) and 882 differentially expressed metabolites (DAMs) were identified in the leaves of salt-tolerant germplasm LQ under salt stress, whereas the sensitive germplasm DT had 1632 DEGs and 797 DAMs, respectively. Differential genes and metabolites were involved in metabolic pathways such as flavonoid biosynthesis, isoquinoline alkaloid synthesis, and phenylalanine metabolism. In particular, LQ alleviated salt stress damage and enhanced salt tolerance by increasing oxidase activities in its flavonoid and phenylalanine metabolic pathways and regulating the expression of key genes and enzymes. This study provides valuable insights and empirical data to support the selection of appropriate Astragalus mongholicus germplasms for saline regions and the development of improved cultivars. Full article

Gelling agents are critical for food texture and stability; usually, polymeric substances are employed. Low-molecular-weight gelators (LMWG) like phenylalanine (PHE) form supramolecular gels. However, food applications are limited due to amino acid derivatization or gelling solvent. This study characterizes PHE, water, and propylene glycol solutions and their gelling capability when cooled or stirred. Gelation is faster at higher stirring speeds. Gel strength increases if pH is near the PHE isoelectric point or at higher PHE concentrations, which increases gel transition temperature. Solutions develop browning in xylose (XYL) presence via first-order kinetics, accelerated by increasing PHE or xylose concentration. Full article

Hyaluronic acid (HA), a natural polymer produced through biotechnological processes, is initially synthesized with a high molecular weight, which is subsequently reduced for specific applications. This work aims to develop an experimental laboratory device that enables the controlled depolymerization of HA to achieve a targeted molecular weight. This is accomplished by applying precisely regulated temperature and pressure conditions that facilitate the cleavage of HA polymer chains as they pass through a narrow capillary. The process also allows for a controlled exposure time to elevate the temperature and pressure, with the rapid transition between standard and elevated conditions ensuring temporal stability. A key innovation of this approach is the selective application of an elevated temperature to a designated capillary section, adjustable from 0.5 to 5 m in 0.5 m increments, allowing for a broad range of reaction times. Numerical simulations verified temperature distribution along the capillary during heating and cooling. The device’s effectiveness is demonstrated by cleaving HA chains (initial Mw = 2150 kDa) dissolved in an aqueous solution at a 0.1 mg/mL concentration. Results from a factorial experiment that evaluated the extremes of three main variables show cleavage across a wide molecular weight range, reaching values as low as 8 kDa, with a variance of less than 5%. This study presents a viable device for the selective depolymerization of HA via physical parameters alone, eliminating the need for additional substances such as acids, hydroxides, or enzymes. Full article

Aquatic products contain a large amount of protein, which can promote the production of a variety of biogenic amines through the function of microorganisms. Biogenic amines are a broad category of organic substances that contain nitrogen and have a low molecular weight. The presence of biogenic amines can cause the deterioration and excessive accumulation of aquatic products, which can cause damage to human health. Therefore, it is essential to discover a fast, convenient, and easy to operate method for the determination of biogenic amines in aquatic products. In this paper, the function and research significance of biogenic amines are analyzed from the aspects of their formation, toxicological properties, harm to the human body, and control methods. Several common direct detection techniques and indirect techniques for biogenic amines are briefly introduced especially sensors. This review provides references for efficient detection in the future. Full article

Oleogels (organogels) are systems resembling a solid substance based on the gelation of organic solvents (oil or non-polar liquid) through components of low molecular weight or oil-soluble polymers. Such compounds are organogelators that produce a thermoreversible three-dimensional gel network that captures liquid organic solvents. Oleogels based on natural oils are attracting more attention due to their numerous advantages, such as their unsaturated fatty acid contents, ease of preparation, and safety of use. As a result of the research, two oleogels were developed, into which freeze-dried alginate carriers with a probiotic, L. casei, were incorporated. Two techniques were used to produce probiotic-loaded capsules—extrusion and emulsification. Alginate beads obtained by the extrusion process have a size of approximately 1.2 mm, while much smaller microspheres were obtained using the emulsification technique, ranging in size from 8 to 17 µm. The trehalose was added as a cryoprotectant to improve the survival rate of probiotics in freeze-dried alginate carriers. The encapsulation efficiency for both of the methods applied, the emulsification and the extrusion technique, was high, with levels of 90% and 87%, respectively. The obtained results showed that the production method of probiotic-loaded microspheres influence the bacterial viability. The better strain survival in the developed systems was achieved in the case of microspheres produced by the emulsification (reduction in bacterial cell viability in the range of 1.98–3.97 log in silica oleogel and 2.15–3.81 log in sucragel oleogel after 7 and 30 days of storage) than by the extrusion technique (after a week and a month of oleogel storage, the decrease in cell viability was 2.52–4.52 log in silica oleogel and 2.48–4.44 log in sucragel oleogel). Full article

This investigation aimed to assess the in vitro and in silico biological properties of the ethyl acetate (EtOAc) extract obtained from leaves of Rubus ulmifolius Schott collected in Algeria. The phytochemical screening data disclosed that flavonoids, tannins, coumarins, saponins, and anthocyanins were abundant. High levels of total phenolics, total flavonoids and flavonols (523.25 ± 3.53 µg GAE/mg, 20.41 ± 1.80, and 9.62 ± 0.51 µg QE/mg respectively) were detected. Furthermore, GC-MS analysis was performed to identify low molecular weight compounds. d-(-)-Fructofuranose, gallic acid, caffeic acid, and catechin were detected as main metabolites of the EtOAc extract. The outcomes revealed that the extract exerted a potent antioxidant apt, and ensured significant bacterial growth inhibitory capacity, where the inhibition zone diameters ranged from 20.0 ± 0.5 to 24.5 ± 0.3 mm. These outcomes were confirmed through molecular docking against key bacterial enzymes that revealed significant interactions and binding affinities. d-(-)-Fructofuranose was identified as the most polar and flexible compound. Gallic acid and caffeic acid demonstrated higher unsaturation. Caffeic acid was well absorbed in the blood–brain barrier (BBB) and human intestine. Catechin was well absorbed in CaCO₃, and can act as an inhibitor of CYP1A2. These results highlight how crucial it is to keep looking into natural substances in the quest for more potent and targeted pathology therapies. Full article