Determination of relative bioavailability of copper from copper glycinate in growing beef steers.

Chelated copper (Cu) sources, such as Cu glycinate (CuGly), may be more bioavailable relative to Cu sulfate (CuSO 4 ) when fed to ruminants under antagonistic pressure. The objective of this study was to determine the bioavailability of CuGly (GemStone Cu; Phibro Animal Health) relative to CuSO4 in steers fed a diet supplemented with 0.3% sulfur and 2 mg molybdenum/kg of dry matter (DM). Sixty Angus crossbred steers (n = 12 per treatment) averaging 288 ±â€…4.85 kg were enrolled in a 90-d study and fed a corn silage-based diet with one of five Cu supplementation strategies, including no supplemental Cu (CON), 5 or 10 mg supplemental Cu from CuSO4/kg DM, and 5 or 10 mg supplemental Cu from CuGly/kg DM. Steers were housed in pens equipped with GrowSafe feed bunks (GrowSafe Systems Ltd., Airdire, AB, Canada), with six steers per pen. Growth performance, liver Cu, and plasma Cu were analyzed in the MIXED procedure of SAS 9.4 (SAS Inst. Inc, Cary, NC) with orthogonal contrasts to compare CON vs. 5 mg Cu/kg DM, CON vs. 10 mg Cu/kg DM, 5 vs. 10 mg Cu/kg DM, and CuSO4 vs. CuGly. Copper indices were regressed against Cu intake and slopes were calculated using the GLM procedure SAS. Dietary Cu supplementation did not affect steer body weights on days 0, 28, 56, or 90 (P ≥ 0.52), average daily gain, dry matter intake, or gain:feed (P ≥ 0.36). Final plasma Cu concentration did not differ between CON vs. 5 mg Cu/kg DM (P = 0.79), CON vs. 10 mg Cu/kg DM (P = 0.65), or 5 vs. 10 mg Cu/kg DM (P = 0.39). Steers receiving CuSO4 tended to have greater final plasma Cu concentrations than those receiving CuGly (P = 0.08). Initial liver Cu concentration averaged 374 mg Cu/kg DM, which is considered highly adequate. No steers reached deficient Cu status by the end of the 90-d period. Control steers had lesser final liver Cu concentrations than supplemented steers (P ≤ 0.04). Steers receiving 10 mg supplemental Cu/kg DM had greater liver Cu concentrations than those receiving 5 mg supplemental Cu/kg DM (P = 0.01). Copper source had no effect on final liver Cu concentrations (P = 0.57) and based on liver Cu and Cu intake the bioavailability of CuGly was similar to CuSO4 (115%; P = 0.27). The initially high Cu status and the fact that cattle did not become Cu deficient may have impacted the relative bioavailability results, and more research is needed to investigate the role initial Cu status and antagonistic pressure play in the bioavailability of chelated Cu sources.

Effects of L-Methionine and DL-Methionine on Growth Performance, Methionine-Metabolizing Enzyme Activities, Feather Traits, and Intestinal Morphology of Medium-Growing, Yellow-Feathered Chickens between 1 and 30 Days of Age.

This experiment investigated the effects of L-Methionine (L-Met) on growth performance, Met-metabolizing enzyme activity, feather traits, and small intestinal morphological characteristics, and compared these with DL-Methionine (DL-Met) for medium-growing, yellow-feathered broilers during the starter phase. Furthermore, the aim was to provide recommendations for the appropriate dietary Met levels in feed. A total of 1584 1-d broilers were randomly divided into 11 treatment groups with six replicates of 24 birds each: basal diet (CON, Met 0.28%), basal diet + L-Met (0.04%, 0.08%, 0.12%, 0.16%, 0.20%), and basal diet + DL-Met (0.04%, 0.08%, 0.12%, 0.16%, 0.20%). The total trial period was 30 days. Compared with broilers fed the basal diet, those fed 0.04 to 0.20% supplemental Met had higher final body weight (FBW), average daily feed intake (ADFI), average daily gain (ADG), and lower feed-to-gain ratio (F: G) (p < 0.05). Compared with DL-Met groups, the L-Met group had higher FBW and ADG (p < 0.05). The relative bioavailability (RBV) of L-Met in ADG of 1-30 d was 142.5%. Chicks fed diets supplemented with L-Met had longer fourth primary feather lengths compared to birds fed the control and diets supplemented with DL-Met (p < 0.05). Compared to the control, birds supplemented with DL-Met or L-Met had an increased moulting score (p ≤ 0.05). Chicks fed diets supplemented with L-Met had lower activities of methionine adenosyl transferase (MAT) compared to those fed the basal diet or supplemented with DL-Met (p < 0.05). Chicks supplemented with either DL-Met or L-Met had higher activities of cystathionine ß-synthase (CBS) than those fed the basal diet (p < 0.05). Compared with the control, chicks fed diets supplemented with either DL-Met or L-Met had an enhanced level of albumin in plasma (p < 0.05). There were no obvious differences in the plasma content of uric acid and total protein among the treatments (p > 0.05). Chicks fed diets supplemented with either DL-Met or L-Met had higher villus height and V/C in the duodenal than chicks fed the basal diet (p < 0.05). The jejunum morphology was not affected by either L-Met or DL-Met supplementation (p > 0.05). Therefore, dietary supplementation with DL-Met or L-Met improved the growth performance, feather traits, and intestinal morphological characteristics of medium-growing, yellow-feathered broiler chickens aged 1 to 30 d by decreasing the enzyme activities of Met methylation (MAT) and increasing the enzyme activities of the sulfur transfer pathway (CBS), and supplementation with L-Met showed a better improvement compared with DL-Met. The relative efficacy of L-Met to DL-Met was 142.5% for ADG of yellow-feathered broilers. The appropriate Met levels for medium-growing, yellow-feathered broilers are between 0.36~0.38% (supplementation with DL-Met) or 0.32~0.33% (supplementation with L-Met) when based on ADG and feed-to-gain ratio.

Status of the transfer state of 137Cs in zooplankton and surface water fish off Fukushima during 2018-2021.

Radiocaesium introduced to coastal waters by the accident at the Fukushima Dai-ichi Nuclear Power Station (F1NPS) elevated the radioactivity level in biota. The radionuclide level in zooplankton, concentration of 137Cs radioactivity in surface water fish decreased rapidly, which was the primary food source for planktivorous fish, was recognized as not to be depurated at the same level prior to the accident. To evaluate the possible cause of this phenomenon, zooplankton and surface water fish were collected off Fukushima during 2018-2021, and the presence of radioactive particles was also examined. The concentrations of stable Cs and 137Cs radioactivity were analysed along with aluminium which was an indicator element of Cs that originated from suspended particles which were attached to or ingested by zooplankton. As a result, radioactive particles were often found in coastal zooplankton samples, and stable Cs and 137Cs of this inorganic fraction were identified. After removal of this excess radioactivity, the 137Cs radioactivity in whole-body tissue of zooplankton was derived. However, the level in the soft part of zooplankton during 2018-2020 was still greater than the levels which existed before 2010. Since habitat seawater was understood to not be a substantial source of 137Cs, then 137Cs transfer along the food chain, possibly from phytoplankton or detritus of enhanced radioactivity were suggested as important sources of 137Cs. In addition, enhanced 137Cs radioactivity in zooplankton was considered consequently elevate radioactivity levels in surface-dwelling water fish off Fukushima. Although the radioactivity level was not radiologically significant in relation to seafood safety limit, enhanced 137Cs radioactivity levels in biota was demonstrated in southern waters off Fukushima. In contrast, derived 137Cs/133Cs atom ratios of fish and seawater south of 37°E and west from 142°E indicated that radiocaesium transfer between fish and the environment was in an equilibrium state, showing the environment beyond these geographical coordinates had returned to the pre-accident state.

Preliminary Evaluation of Historical used Pesticides in Quercus robur Wood in Belgium: a Negative Finding.

Historically used pesticides poses a threat to biodiversity while their release pathways remain unclear. Trees could be a potential release source due to their long lifespan. This study examined 38 samples to assess pesticide concentrations in pedunculate oak from Belgium. Low concentrations of procymidone were detected in two samples from one stump. Our findings suggest that accumulations of historically used pesticides in pedunculate oaks within forests are improbable. We conclude that leaving dead wood poses no risks for pesticide release to the environment. However, further research involving diverse tree species and regions is needed to refine and validate this conclusion.

Selenium spatial distribution and bioavailability of soil-plant systems in China: a comprehensive review.

Selenium (Se) has a dual nature, with beneficial and harmful effects on plants, essential for both humans and animals, playing a crucial role in ecosystem regulation. Insufficient Se in specific terrestrial environments raises concerns due to its potential to cause diseases, while excess Se can lead to severe toxicity. Thus, maintaining an optimal Se level is essential for living organisms. This review focuses first on Se transformation, speciation, and geochemical properties in soil, and then provides a concise overview of Se distribution in Chinese soil and crops, with a focus on the relationship between soil Se levels and parent materials. Additionally, this paper explores Se bioavailability, considering parent materials and soil physicochemical properties, using partial least squares path modeling for analysis. This paper aimed to be a valuable resource for effectively managing Se-enriched soil resources, contributing to a better understanding of Se role in ecosystems.

Functional foods lipids: unraveling their role in the immune response in obesity.

Functional lipids are lipids that are found in food matrices and play an important role in influencing human health as their role goes beyond energy storage and structural components. Ongoing research into functional lipids has highlighted their potential to modulate immune responses and other mechanisms associated with obesity, along with its comorbidities. These lipids represent a new field that may offer new therapeutic and preventive strategies for these diseases by understanding their contribution to health. In this review, we discussed in-depth the potential food sources of functional lipids and their reported potential benefit of the major lipid classification: based on their composition such as simple, compound, and derived lipids, and based on their function such as storage and structural, by investigating the intricate mechanisms through which these lipids interact in the human body. We summarize the key insights into the bioaccessibility and bioavailability of the most studied functional lipids. Furthermore, we review the main immunomodulatory mechanisms reported in the literature in the past years. Finally, we discuss the perspectives and challenges faced in the food industry related to functional lipids.

Functional lipids are immunomodulatory agents in chronic non-communicable diseases.Bioaccessibility and bioavailability depend mainly on the lipid profile and the matrix food.Incorporation of polyunsaturated fat in foods is a current technological challenge.Emerging technologies are good options for extracting functional lipids efficiently.Nanotechnology plays an important role in developing food delivery systems.Food delivery systems improve the bioavailability of functional lipids.

Bioactivity and Bioavailability of Carotenoids Applied in Human Health: Technological Advances and Innovation.

This article presents a groundbreaking perspective on carotenoids, focusing on their innovative applications and transformative potential in human health and medicine. Research jointly delves deeper into the bioactivity and bioavailability of carotenoids, revealing therapeutic uses and technological advances that have the potential to revolutionize medical treatments. We explore pioneering therapeutic applications in which carotenoids are used to treat chronic diseases such as cancer, cardiovascular disease, and age-related macular degeneration, offering novel protective mechanisms and innovative therapeutic benefits. Our study also shows cutting-edge technological innovations in carotenoid extraction and bioavailability, including the development of supramolecular carriers and advanced nanotechnology, which dramatically improve the absorption and efficacy of these compounds. These technological advances not only ensure consistent quality but also tailor carotenoid therapies to each patient's health needs, paving the way for personalized medicine. By integrating the latest scientific discoveries and innovative techniques, this research provides a prospective perspective on the clinical applications of carotenoids, establishing a new benchmark for future studies in this field. Our findings underscore the importance of optimizing carotenoid extraction, administration, bioactivity, and bioavailability methods to develop more effective, targeted, and personalized treatments, thus offering visionary insight into their potential in modern medical practices.

Hemoglobin Regeneration Efficiency and Relative Iron Bioavailability of Four Elemental Iron Powders in Rats.

Effective food fortification strategies using elemental iron powders (EIPs) are needed to combat iron deficiency anemia. The purpose of this study was to determine hemoglobin regeneration efficiency (HRE) and relative iron bioavailability (RBV) of four food-grade EIPs (El-Lyte (EL), Hi-Sol (HS), H-325 (H3), and A-131 (A1)) by treating anemic rats with 14 d iron repletion diets (uncooked and cooked), fortified with a 12, 24, or 36 mg iron/kg diet of the EIPs, ferrous sulfate monohydrate (FS, FeSO4•H2O), or no added iron (control), n = 9-12/group. The ability of EL and HS to maintain hemoglobin for 6 weeks on the 6 mg iron/kg diet was also studied. The dissolution rate of iron from the EIPs was measured in hydrochloric acid at pH 1.0. Compared to FS, the EL, HS, and A1 EIPs had >50% overall RBV, with the following order: HS > A1 > EL > H3 (p ≤ 0.05); the effect of cooking was not significant (p > 0.05). Dissolution testing revealed that the mean RBV of the EIPs was positively associated with the percentage of iron solubility. In the 6-week maintenance study, EL and HS maintained hemoglobin as well as FS. Overall, the findings show that at the concentrations of iron tested, these EIPs are effective fortification agents to replenish hemoglobin and correct iron deficiency anemia.

The Antiviral Potential of Perilla frutescens: Advances and Perspectives.

Viruses pose a significant threat to human health, causing widespread diseases and impacting the global economy. Perilla frutescens, a traditional medicine and food homologous plant, is well known for its antiviral properties. This systematic review examines the antiviral potential of Perilla frutescens, including its antiviral activity, chemical structure and pharmacological parameters. Utilizing bioinformatics analysis, we revealed the correlation between Perilla frutescens and antiviral activity, identified overlaps between Perilla frutescens target genes and virus-related genes, and explored related signaling pathways. Moreover, a classified summary of the active components of Perilla frutescens, focusing on compounds associated with antiviral activity, provides important clues for optimizing the antiviral drug development of Perilla frutescens. Our findings indicate that Perilla frutescens showed a strong antiviral effect, and its active ingredients can effectively inhibit the replication and spread of a variety of viruses in this review. The antiviral mechanisms of Perilla frutescens may involve several pathways, including enhanced immune function, modulation of inflammatory responses, and inhibition of key enzyme activities such as viral replicase. These results underscore the potential antiviral application of Perilla frutescens as a natural plant and provide important implications for the development of new antiviral drugs.

Conquering the beyond Rule of Five Space with an Optimized High-Throughput Caco-2 Assay to Close Gaps in Absorption Prediction.

Current drug development tends towards complex chemical molecules, referred to as "beyond rule of five" (bRo5) compounds, which often exhibit challenging physicochemical properties. Measuring Caco-2 permeability of those compounds is difficult due to technical limitations, including poor recovery and detection sensitivity. We implemented a novel assay, with optimized incubation and analytics, to measure permeability close to equilibrium. In this setup an appropriate characterization of permeability for bRo5 compounds is achievable. This equilibrated Caco-2 assay was verified with respect to data validity, compound recovery, and in vitro to in vivo correlation for human absorption. Compared to a standard assay, it demonstrated comparable performance in predicting the human fraction absorbed (fa) for reference compounds. The equilibrated assay also successfully characterized the permeability of more than 90% of the compounds analyzed, the majority of which were bRo5 (68%). These compounds could not be measured using the standard assay. Permeability and efflux ratio (ER) were highly predictive for in vivo absorption for a large set of internal bRo5 compounds. Reference cut-offs enabled the correct classification of high, moderate, and low absorption. This optimized equilibrated Caco-2 assay closes the gap for a high-throughput cellular permeability method in the bRo5 chemical space.

Carrier Systems for Advanced Drug Delivery: Improving Drug Solubility/Bioavailability and Administration Routes.

The disadvantages of some conventional drugs, including their low bioavailability, poor targeting efficiency, and important side effects, have led to the rational design of drug delivery systems. In particular, the introduction of drug delivery systems is a potential approach to enhance the uptake of therapeutic agents and deliver them at the right time and in the right amount of concentration at the required site, as well as open new strategies for effective illness treatment. In this review, we provide a basic understanding of drug delivery systems with an emphasis on the use of cyclodextrin-, polymer- and surfactant-based delivery systems. These systems are very attractive because they are biocompatible and biodegradable nanomaterials with multifunctional components. We also provide some details on their design considerations and their use in a variety of medical applications by employing several routes of administration.

Investigation of Stabilized Amorphous Solid Dispersions to Improve Oral Olaparib Absorption.

In this study, we investigated the formulation of stable solid dispersions to enhance the bioavailability of olaparib (OLA), a therapeutic agent for ovarian cancer and breast cancer characterized as a BCS class IV drug with low solubility and low permeability. Various polymers were screened based on solubility tests, and OLA-loaded solid dispersions were prepared using spray drying. The physicochemical properties of these dispersions were investigated via scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier Transform Infrared Spectroscopy (FT-IR). Subsequent dissolution tests, along with assessments of morphological and crystallinity changes in aqueous solutions, led to the selection of a hypromellose (HPMC)-based OLA solid dispersion as the optimal formulation. HPMC was effective at maintaining the supersaturation of OLA in aqueous solutions and exhibited a stable amorphous state without recrystallization. In an in vivo study, this HPMC-based OLA solid dispersion significantly enhanced bioavailability, increasing AUC0-24 by 4.19-fold and Cmax by more than 10.68-fold compared to OLA drug powder (crystalline OLA). Our results highlight the effectiveness of HPMC-based solid dispersions in enhancing the oral bioavailability of OLA and suggest that they could be an effective tool for the development of oral drug formulations.

Improving the Accuracy of Permeability Data to Gain Predictive Power: Assessing Sources of Variability in Assays Using Cell Monolayers.

The ability to predict the rate of permeation of new compounds across biological membranes is of high importance for their success as drugs, as it determines their efficacy, pharmacokinetics, and safety profile. In vitro permeability assays using Caco-2 monolayers are commonly employed to assess permeability across the intestinal epithelium, with an extensive number of apparent permeability coefficient (Papp) values available in the literature and a significant fraction collected in databases. The compilation of these Papp values for large datasets allows for the application of artificial intelligence tools for establishing quantitative structure-permeability relationships (QSPRs) to predict the permeability of new compounds from their structural properties. One of the main challenges that hinders the development of accurate predictions is the existence of multiple Papp values for the same compound, mostly caused by differences in the experimental protocols employed. This review addresses the magnitude of the variability within and between laboratories to interpret its impact on QSPR modelling, systematically and quantitatively assessing the most common sources of variability. This review emphasizes the importance of compiling consistent Papp data and suggests strategies that may be used to obtain such data, contributing to the establishment of robust QSPRs with enhanced predictive power.

Refined Cumulative Risk Assessment of Pb, Cd, and as in TCM Decoction Based on Bioavailability through In Vitro Digestion/MDCK Cells.

In this study, the oral bioavailability of Pb, Cd, and As in three types of traditional Chinese medicines (TCMs) and TCM decoctions were investigated through in vitro PBET digestion/MDKC cell model. Furthermore, a novel cumulative risk assessment model associated with co-exposure of heavy metal(loid)s in TCM and TCM decoction based on bioavailability was developed using hazard index (HI) for rapid screening and target organ toxicity dose modification of the HI (TTD) method for precise assessment. The results revealed that the bioavailability of Pb, Cd, and As in three types of TCM and TCM decoction was 5.32-72.49% and 4.98-51.97%, respectively. After rapid screening of the co-exposure health risks of heavy metal(loid)s by the HI method, cumulative risk assessment results acquired by TTD method based on total metal contents in TCMs indicated that potential health risks associated with the co-exposure of Pb, Cd, and As in Pheretima aspergillum (E. Perrier) and Oldenlandia diffusa (Willd.) Roxb were of concern. However, considering both the factors of decoction and bioavailability, TTD-adjusted HI outcomes for TCMs in this study were <1, indicating acceptable health risks. Collectively, our innovation on cumulative risk assessment of TCM and TCM decoction provides a novel strategy with the main purpose of improving population health.

Validation of the analytical methodology used in obtaining the oral bioavailability of organic target pollutants in atmospheric particulate matter (PM10) applying an in-vitro method.

In recent years, scientists have started evaluating the portion of PM-bound pollutants that may be liberated (bioaccessible fraction) in human fluids and spread through the digestive system ultimately entering systemic circulation (known as the bioavailable fraction). In the current research, an analytical procedure was validated and applied to characterize the oral bioavailable fraction of PM10 samples. The approach encompassed the determination of 49 organic contaminants. The proposed method aims to biomimetic complete mouth-gastric-intestinal system basing on an adaptation of the unified bioaccessibility method (UBM) modified by the inclusion of a dialysis membrane to mimic intestinal absorption and obtain the orally bioavailable fractions. It was followed by a vortex-assisted liquid-liquid extraction (VALLE) step, using gas chromatography-tandem mass spectrometry (GC-MS/MS). Analytical procedure was effectively validated by employing selected reaction monitoring (SRM) mode in MS/MS, matrix-matched calibration, and deuterium-labelled surrogate standards. This approach ensured heightened sensitivity, minimized matrix effects, and compensated for any losses during the process. The validation process covered various aspects, including studying linearity, determining detection and quantification limits, assessing analytical recoveries at three concentration levels, and evaluating precision both within a single day and across multiple days. The validated method was applied to PM10 samples, revealing that polycyclic aromatic hydrocarbons (PAHs) were the most frequently detected, with significant seasonal variations in their concentrations. Organophosphorus flame retardants (OPFRs) like TCPP were also detected in bioavailable fractions, highlighting their potential health impact. Bisphenols, SMCs, and PAEs were not detected, suggesting low levels in the studied urban area. Further research is needed to understand the bioavailability of PM-bound pollutants in different environments.

Comparison of two self-nanoemulsifying drug delivery systems using different solidification techniques for enhanced solubility and oral bioavailability of poorly water-soluble celecoxib.

In this study, we aimed to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) and a solid self-nanoemulsifying granule system (S-SNEGS) to enhance the solubility and oral bioavailability of celecoxib. This process involved the preparation of a liquid SNEDDS (L-SNEDDS) and its subsequent solidification into a S-SNEDDS and a S-SNEGS. The L-SNEDDS consisted of celecoxib (drug), Captex® 355 (Captex; oil), Tween® 80 (Tween 80; surfactant) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS; cosurfactant) in a weight ratio of 3.5:25:60:15 to produce the smallest nanoemulsion droplet size. The S-SNEDDS and S-SNEGS were prepared with L-SNEDDS/Ca-silicate/Avicel PH 101 in a weight ratio of 103.5:50:0 using a spray dryer and 103.5:50:100 using a fluid bed granulator, respectively. We compared the two novel developed systems and celecoxib powder based on their solubility, dissolution rate, physicochemical properties, flow properties and oral bioavailability in rats. S-SNEGS showed a significant improvement in solubility and dissolution rate compared to S-SNEDDS and celecoxib powder. Both systems had been converted from crystalline drug to amorphous form. Furthermore, S-SNEGS exhibited a significantly reduced angle of repose, compressibility index and Hausner ratio than S-SNEDDS, suggesting that S-SNEGS was significantly superior in flow properties. Compared to S-SNEDDS and celecoxib powder, S-SNEGS increased the oral bioavailability (AUC value) in rats by 1.3 and 4.5-fold, respectively. Therefore, S-SNEGS wolud be recommended as a solid self-nanoemulsifying system suitable for poorly water-soluble celecoxib.

Intranasal delivery of doxepin: enhancing brain targeting efficiency utilizing nanostructured lipid carriers for a biopharmaceutics drug disposition classification system class-I drug.

Doxepin, a Class-I Biopharmaceutics Drug Disposition Classification System (BDDCS) drug, exhibits poor bioavailability due to extensive first-pass metabolism. This research focuses on enhancing the delivery of doxepin by formulating nanostructured lipid carriers (NLCs) through the utilization of the Box-Behnken Design methodology. These optimized NLCs are intended for intranasal administration, with the ultimate goal of improving nose-to-brain drug delivery. NLCs were formulated using a high-speed homogenization technique. The optimized batch had a small particle size (75.80 ± 5.48 nm, PDI = 0.286), high entrapment efficiency (94.10 ± 0.16%), and sustained ex vivo release (82.25 ± 4.61% at 24 h). Characterization studies confirmed the conversion of doxepin from a crystalline to an amorphous state with uniform distribution in the lipid matrix. In vivo pharmacokinetic studies in rats showed significantly higher doxepin concentration in the brain tissue (Cmax = 16.77 µg/g, tmax = 30 min) after intranasal administration compared to intravenous administration (Cmax = 2.53 µg/g, tmax = 6 h). High-drug targeting efficiency (DTE = 284.3%) and direct transport percentage (DTP = 64.8%) suggested direct penetration of NLCs in the brain via olfactory and trigeminal pathways. In conclusion, the study highlights the potential of NLCs to improve the bioavailability of doxepin through nose-to-brain delivery and thereby potentially enable the treatment of neurological disorders.

A simple and sensitive LC-MS/MS method for the determination of loganic acid in rat plasma and its pharmacokinetic analysis.

Loganic acid is an iridoid compound extracted from Gentianaceae plant Gentiana macrophylla Pall. It can effectively inhibit inflammation and tumor migration and has antioxidant activity. In this paper, we establish a simple, fast, sensitive and validated LC-MS method with the purpose of quantification of loganic acid in rat plasma with gliclazide as an internal standard (IS). Methanol was used to precipitate the protein in the plasma sample, and a C18 column (2.1 × 50 mm, 1.7 µm) was used for the separation of the target compound. Meanwhile, 0.1% formic acid water-methanol was employed as the mobile phase. Multiple reaction monitoring detection mode was adopted in detection with m/z 375.1 > 213.2 for loganic acid and m/z 322.1 > 169.9 for the IS, respectively, in negative ion scan mode. The linear range of calibration curve was 5.77-11,540.00 ng/ml, and the lower limit of detedtion was 2.89 ng/ml. The inter-day and intra-day precision and accuracy were <15% for lower limit of quantitation, low, middle and high quality control samples. This method was successfully used for the pharmacokinetic study of loganic acid in rat plasma at a dose range of 50-150 mg/kg for oral administration and 2 mg/kg for intravenous administration. The pharmacokinetic results showed that the oral bioavailability of loganic acid was low (2.71-5.58%).

Synthesis, Antimicrobial, Molecular Docking Against Bacterial and Fungal Proteins and In Silico Studies of Glucopyranoside Derivatives as Potent Antimicrobial Agents.

Carbohydrate derivatives play a crucial role in biochemical and medicinal research. Therefore, the present study was designed to explore the synthesis of methyl α-D-glucopyranoside derivatives (1, MDG), focusing on their efficacy against bacterial and fungal infections. The structure of the synthesized compounds was ascertained using spectral and elemental analyses. Antimicrobial screening revealed strong antifungal properties and exhibited MIC values of 16-32 µg/L and MBC 64-128 µg/L. Structure-activity relationship (SAR) analysis indicated that adding nonanoyl and decanoyl groups to ribose moiety enhanced potency against both bacterial and fungal strains. Compounds 6 and 7, presented nonanoyl and decanoyl substituents and demonstrated greater efficacy. In addition, DFT studies identified compound 8 as possessing ideal electronic properties. Molecular docking revealed that compound 8 exhibits exceptional binding affinities to bacterial proteins, conferring potent antibacterial and antifungal activities. In addition, pharmacokinetic optimization via POM analysis highlighted compounds 1 and 2 as promising bioavailable drugs with minimal toxicity. Molecular dynamics simulations confirmed the stability of the 2-S. aureus complex, revealing the therapeutic potential of compounds 2 and 8. The integration of in vitro and in silico methods, including DFT anchoring dynamics and molecular dynamics simulations, provides a solid framework for the advancement of effective anti-infective drugs.