High-performance Liquid Chromatography Research Articles

Determining the Pharmacokinetic Properties of Two Different Doses of Meloxicam in Barred Owls (Strix varia)

Anthropogenic activities have negatively affected many birds, including owls. The Wildlife Hospital of Louisiana (WHL) has seen a 3.2-fold increase in barred owl (Strix varia) cases over the past eight years (2023, 134; 2015, 42). Because most of these animals present with traumatic injuries, analgesics should be considered in their treatment plan. To date, no study has measured the pharmacokinetics of an analgesic in barred owls. The goals of this study were to determine the harmonic means, times to maximum concentration, and elimination half-lives for single 1 mg/kg and 2 mg/kg intramuscular doses of meloxicam. Twelve barred owls (1 mg/kg, n = 6; 2 mg/kg, n = 6) admitted to the WHL and determined to be clinically normal based on examination and blood work were recruited for this study. Meloxicam was administered intramuscularly, and blood samples were collected intermittently over 12 h to measure plasma concentrations using high-performance liquid chromatography. Both doses had rapid elimination half-lives (1 mg/kg, 0.99 ± 0.1 h; 2 mg/kg, 1.07 ± 0.43 h) and were below the limits of quantification (0.1 µg/mL) by 6–12 h. Based on these results, 1 and 2 mg/kg doses of meloxicam were found to produce plasma concentrations below therapeutic concentrations for less than four hours, making current twice-daily recommended dosing intervals unlikely to provide desired analgesia.

Determination of PAH Contamination in Breast Milk Samples from Hungarian Volunteering Mothers, Using HPLC–FLD

(1) The evidence is mounting that polycyclic aromatic hydrocarbons (PAHs) are a class of hazardous organic compounds with established carcinogenic and toxic properties. Humans may be exposed to PAHs through several different routes, including diet, inhalation, and dermal contact. There is also a possibility that they could transfer into breast milk following maternal exposure, which could potentially endanger breastfeeding infants. (2) The objective of this study was to ascertain the concentration of polycyclic aromatic hydrocarbons (PAHs) in breast milk samples from 50 Hungarian mothers, employing high-performance liquid chromatography with fluorescence detection (HPLC–FLD). An Incremental Life Risk Calculation (IRCL) model estimated the carcinogenic risk to infants. (3) Total PAH concentrations ranged from 0 to 78 ng/mL, with fluorene (5.3 ng/mL), phenanthrene (3.2 ng/mL), and pyrene (2.5 ng/mL) being the most abundant. PAHs were detected in 48 of the 50 samples, with phenanthrene present in 92% of samples. Dibenzo (a,h)anthracene was not detected. (4) According to the model measurements, most of the samples were within acceptable risk levels; however, 2 samples out of 50 posed a higher risk. Statistical analysis of questionnaires completed by the mothers indicated that factors such as diet, residence, and education may influence PAH levels in breast milk.

Fabrication of a molecularly imprinted poly(methyl methacrylate) decorated graphite electrode for detection of aloe emodin in Aloe vera

In this work, the authors represent a comprehensive approach for the development and validation of a novel graphite-supported molecularly imprinted poly(methyl methacrylate) electrode for the selective and sensitive detection of aloe emodin (AE) in aloe-based cosmetic products. The electrocatalytic activity of the electrode was evaluated using cyclic voltammetry and differential pulse voltammetry techniques in phosphate buffer saline. Surface morphology, structural characteristics, and imprinting endorsement were investigated using field emission scanning electron microscopy, Fourier-transform infrared spectroscopy, and UV-Vis spectroscopy. Under the optimal conditions, the electrode showed an oxidative differential pulse voltammetry peak at -0.2931±0.011 V (vs. Ag/AgCl, saturated KCl). The current was increased linearly with increasing concentrations of AE from 0.0005 to 350 µM, with a low detection limit of 0.0003 µM. The voltammetric analysis has been validated by reverse-phase high-performance liquid chromatography (RP-HPLC) methods. A partial least square regression model was developed to correlate the results obtained from the proposed system with the reference values obtained by RP-HPLC. The model showed a high prediction accuracy of 95.95 % for the detection of AE in cosmetic samples. The developed electrode provides a low-cost, rapid, easy, and convenient method for the detection of AE in cosmetic products, offering potential benefits for quality control and safety assessment in the cosmetic industry.

Ambient Air-Synthesized CsPbBr3 Nanocrystals Coupled with TiO2 Film as an Efficient Hybrid Photoanode for Photoelectrochemical Methanol-to-Formaldehyde Conversion.

Due to its exceptional optoelectronic properties in the visible spectrum, cesium lead bromide (CsPbBr3) perovskite has attracted considerable attention in solar-driven organic transformations via photoelectrochemical (PEC) cells. However, the performance of the devices is adversely affected by electron-hole recombination occurring between a transparent conductive substrate, such as fluorine-doped tin dioxide (FTO), and a perovskite layer. Herein, to mitigate this issue, a compact layer of titanium dioxide (TiO2) was employed as both an electron transport layer and a hole blocking layer to diminish charge recombination while facilitating electron transfer in such perovskite material. At the oxidation peak potential of 0.70 V vs Ag/AgNO3, a hybrid photoanode of CsPbBr3/TiO2/FTO exhibited a significant increase in photocurrent density, from 15 to 41 μA/cm2, compared to a configuration without a TiO2 layer. Furthermore, the introduction of methanol as a hole scavenger in the PEC system using the hybrid photoanode facilitated the separation of electron-hole pairs, which led to an enhanced photocurrent density of 60 μA/cm2 and promoted the production of formaldehyde. High-performance liquid chromatography (HPLC) confirmed the generation of formaldehyde at a concentration of 26.69 μM with a Faradaic efficiency of 92% under an applied potential of 0.50 V vs Ag/AgNO3 for 60 min of PEC reaction. In addition to the enhanced PEC performance achieved from this hybrid photoanode, CsPbBr3 nanocrystals (NCs) in this work were synthesized by the modified one-pot method under ambient air, where highly uniform and high-purity NCs were obtained. This work signifies the groundbreaking exploration of CsPbBr3 NCs with TiO2 as a photoelectrode material in the organic-based PEC cells, which efficiently improved the interfacial charge transfer within the photoanode for the conversion of methanol to formaldehyde, marking a significant advancement in the field.

Structural Characterization and Antioxidant Activity of Exopolysaccharide Produced from Beet Waste Residue by Leuconostoc pseudomesenteroides

Lactic acid bacteria exopolysaccharide (EPS) is a large molecular polymer produced during the growth and metabolism of lactic acid bacteria. EPS has multiple biological functions and is widely used in fields such as food and medicine. However, the low yield and high production cost of EPS derived from lactic acid bacteria limit its widespread application. In this study, we used beet waste residue as a substrate to produce EPS by fermentation with Leuconostoc pseudomesenteroides to improve the utilization rate of agricultural waste and reduce the production cost of lactic acid bacterial EPS. After purification, the molecular weight (Mw) of EPS was determined to be 417 kDa using high-performance size exclusion chromatography (HPSEC). High-performance liquid chromatography (HPLC), Fourier transform infrared (FTIR) spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy revealed that the EPS was composed of glucose subunits with α-1,6 glycosidic linkages. The thermal analysis and heavy metal adsorption capacity revealed a relatively high degradation temperature of 315.54 °C and that the material could effectively adsorb Cu2+. Additionally, the findings indicated that the EPS exhibited a significant ability to neutralize free radicals, a property that was found to be concentration dependent. Furthermore, the results of the intracellular study showed the protective effect of freshly isolated EPS on tBHP-induced cellular oxidative stress at a concentration of 50 µg/mL. These results suggest that the EPS from L. pseudomesenteroides may be developed as antioxidant agents for functional food products and pharmaceutical applications due to its capacity to scavenge free radicals.

Determination of 3-hydroxyanthranilic acid in the sweat of healthy older adults

3-Hydroxyanthranillic acid (3HAA) is one of the key metabolites from the tryptophan (TRP) metabolism pathway and is associated with aging, age-associated diseases, and healthy lifespan extension. This study aims to detect 3HAA in the sweat of healthy older adults using simple, high-performance liquid chromatography (HPLC) method. Chromatographic separation using 20 mmol/L sodium acetate, 3 mmol/L zinc acetate, and 7% (v/v) acetonitrile as mobile phase is possible to simultaneous detect 3HAA, KYN, and TRP with UV and fluorescence detection, respectively, under 6 min. This method demonstrated excellent linearity with coefficient of determination (r2) greater than 0.998 for all analytes. The linear range were 0.05–6 µg/mL for TRP, 0.1–6 µg/mL for KYN and 0.2–6 µg/mL for 3HAA. Percentage recoveries from spiked in human sweat ranged from 90 ± 7–101 ± 3 for TRP, 86 ± 1–92 ± 3 for KYN, and 96 ± 1–103 ± 4 for 3HAA. The precision (%RSD) of repeatability and reproducibility is less than 3% and 6%, respectively. This method was used in a cross-sectional study with 81 participants aged 50–79 years, selected randomly from a local primary healthcare hospital’s sampling frame. A detectable amount of 3HAA was observed in all sweat samples, marking the first report of 3HAA presence in human sweat. Additionally, the results revealed that the 3HAA sweat levels increased with age analyzed in three different age groups ranging from 50–59, 60–69, and 70–79. These findings enhance our understanding of sweat profiles and their correlation with aging, potentially further improving early diagnosis, disease monitoring, and development of customized treatment programs for older adults.

Histamine in Fishery: A Five-Year Survey in Northern Italy

Histamine is a biogenic amine and an indicator of fishery product freshness and hygienic quality. The European Regulation EC 2073/2005 sets the standards for fish sample collection and establishes quantitative levels of histamine in fishery products to ensure consumer health and safety. This retrospective study presents data on histamine monitoring in fish and fishery products collected in northern Italy between 2018 and 2022. A total of 138 samples were analysed via enzyme-linked immunosorbent assay (ELISA) and then confirmed by high-performance liquid chromatography with diode-array detection (HPLC-DAD). Four samples found positive contained histamine levels above the legal limit. Monitoring via ELISA and HPLC-DAD can efficiently detect histamine in fish and fishery products and protect consumers’ health.

Coiled Coil Peptide Tiles (CCPTs): Expanding the Peptide Building Block Design with Multivalent Peptide Macrocycles.

Owing to their synthetic accessibility and protein-mimetic features, peptides represent an attractive biomolecular building block for the fabrication of artificial biomimetic materials with emergent properties and functions. Here, we expand the peptide building block design space through unveiling the design, synthesis, and characterization of novel, multivalent peptide macrocycles (96mers), termed coiled coil peptide tiles (CCPTs). CCPTs comprise multiple orthogonal coiled coil peptide domains that are separated by flexible linkers. The constraints, imposed by cyclization, confer CCPTs with the ability to direct programmable, multidirectional interactions between coiled coil-forming "edge" domains of CCPTs and their free peptide binding partners. These fully synthetic constructs are assembled using a convergent synthetic strategy via a combination of native chemical ligation and Sortase A-mediated cyclization. Circular dichroism (CD) studies reveal the increased helical stability associated with cyclization and subsequent coiled coil formation along the CCPT edges. Size-exclusion chromatography (SEC), analytical high-performance liquid chromatography (HPLC), and fluorescence quenching assays provide a comprehensive biophysical characterization of various assembled CCPT complexes and confirm the orthogonal colocalization between coiled coil domains within CCPTs and their designed on-target free peptide partners. Lastly, we employ molecular dynamics (MD) simulations, which provide molecular-level insights into experimental results, as a supporting method for understanding the structural dynamics of CCPTs and their complexes. MD analysis of the simulated CCPT architectures reveals the rigidification and expansion of CCPTs upon complexation, i.e., coiled coil formation with their designed binding partners, and provides insights for guiding the designs of future generations of CCPTs. The addition of CCPTs into the repertoire of coiled coil-based building blocks has the potential for expanding the coiled coil assembly landscape by unlocking new topologies having designable intermolecular interfaces.

Assessing pesticide residue levels in sweetpotato roots and slips treated with fungicides for management of southern blight and circular spot disease caused by Agroathelia rolfsii.

Since 1971, North Carolina (NC) has been the leading sweetpotato-producing state in the United States (US) and is now producing more than half of the nation's annual output. Due to the high demand for US sweetpotatoes from international markets, NC allocates roughly 40% of its sweetpotatoes for export. However, low fungicide residue limits in primary export markets restricts the ability for NC producers to apply fungicides for disease management during sweetpotato production. Agroathelia rolfsii, the causal agent of southern blight and circular spot, is an important pathogen of sweetpotato. Field experiments were conducted in 2022 and 2023 to quantify the residue amount of various active ingredients and transplant-only vs. bedding and transplant applications when managing A. rolfsii in the field. High-performance liquid chromatography analyses of root and vine samples confirmed that none of the tested active ingredients and application timings resulted in residue numbers exceeding the limits of export markets, except for roots treated with thiabendazole. Results from this study provide information for development of application practices with acceptable residue levels for export markets while effectively managing diseases caused by A. rolfsii.

Toxigenic Cyanobacteria and Microcystins in a Large Northern Oligotrophic Lake Onego, Russia

Toxigenic cyanobacteria and microcystins in the oligotrophic pelagic zone and mesotrophic bay of Lake Onego—the second largest lake in Europe—were found for the first time. Microscopic analysis revealed that Dolichospermum lemmermannii, D. circinale and D. spiroides dominated in bloom spots in the oligotrophic zone of the lake and D. flos-aquae and Microcystis aeruginosa OKin the eutrophic bay. The abundance of cyanobacteria in bloom spots is potentially hazardous for humans and animals. PCR-analysis showed that mcyA gene involved in microcystin biosynthesis was found in cyanobacteria of the genera Dolichospermum and Microcystis. Five structural variants of intracellular microcystins were detected in a trace amount using high-performance liquid chromatography–mass-spectrometry of high resolution. The most hazardous hepatotoxin, MC-LR, was found only in the eutrophic bay. In the present study, the reasons for the low cyanotoxin content in the phytoplankton dominated by Dolichospermum are discussed. The findings of our study make a significant contribution to the accumulation of facts which state that toxigenic cyanobacterial blooms can occur in large oligotrophic lakes.

Exploring the Antidiabetic and Antihypertensive Potential of Peptides Derived from Bitter Melon Seed Hydrolysate

Background/Objectives: Type 2 diabetes (T2D) has become a critical global health issue, with an increasing prevalence that contributes to significant morbidity and mortality. Inhibiting dipeptidyl peptidase-IV (DPP4) is a promising strategy for managing T2D. This study aimed to explore the DPP4 inhibitory peptide derived from bitter melon seed protein (BMSP) hydrolysate. Methods: Reversed-phase high-performance liquid chromatography (RP-HPLC) was utilized to fractionate the hydrolysate. Peptide in the highest activity fraction was analyzed using liquid chromatography-mass spectrometry (LC-MS/MS). Peptide synthetic was used for further characterizations, such as bioactivity exploration, inhibition mechanism, molecular docking, and peptide stability against in vitro simulated gastrointestinal (SGI) digestion. Results: The BMSP hydrolysate was digested with gastrointestinal proteases (GP) and assessed for DPP4 inhibitory activity, yielding an IC50 of 1448 ± 105 μg/mL. Following RP-HPLC fractionation, MPHW (MW4) and VPSGAPF (VF7) were identified from fraction F8 with DPP4 IC50 values of 128.0 ± 1.3 µM and 150.6 ± 3.4 µM, respectively. Additionally, MW4 exhibited potential antihypertensive effects through ACE inhibition with an IC50 of 172.2 ± 10.6 µM. The inhibitory kinetics and molecular docking simulations indicated that both MW4 and VF7 were competitive inhibitors of DPP4, while MW4 was also a competitive inhibitor of ACE. Importantly, both peptides remained stable during simulated gastrointestinal digestion, suggesting their resistance to human digestive processes and their capacity to maintain biological activity. Conclusions: The findings suggest that BMSP-GP hydrolysate may have potential in terms of the development of health foods or therapeutic agents. However, in vivo studies are also essential for further confirmation of efficacy.

Evaluation of the Potential of High-Performance Liquid Chromatography–Inductively Coupled Plasma–Mass Spectrometry for the Determination of Chemical Warfare Agents and Their Toxic Degradation Products

The determination of chemical warfare agents (CWAs) and their toxic degradation products (DPs) has become increasingly important for public and military safety in recent years. We focused on assessing the possibility of the HPLC-ICP-MS analytical technique to verify the provisions of the Chemical Weapons Convention. This technique enables the identification and determination of minimal concentrations (ppt range) of elements in various matrices. This fact is important for the determination of CWAs and other highly harmful compounds, even small amounts of which can have serious consequences for living organisms. We have critically analysed the results of scientific research on the identification and quantitative determination of extremely toxic organophosphorus, organosulfur and organoarsenic CWAs, their derivatives and their degradation products using high-performance liquid chromatography (HPLC) coupled with inductively coupled plasma–mass spectrometry (ICP-MS).

Advanced Bio-sensing Technologies for Sickle Cell Disease Diagnosis.

Sickle cell diseases are widespread in regions encompassing the Mediterranean, Middle East, sub-Saharan Africa, and specific parts of Asia, primarily due to the abnormal production of hemoglobin S. This genetic blood disorder stems from a mutation in the beta-globin gene, a crucial component of hemoglobin and the heme-containing protein found in red blood cells. Point mutations in the hemoglobin gene can be inherited as a heterozygous or homozygous pattern. These mutations disrupt the normal configuration of the protein, impeding its physiological function and altering the cell's shape, giving it a sickle-like appearance. The resulting sickle cells can lead to organ damage, intense physical discomfort, and anemia; in severe cases, the condition can be fatal. Early detection and effective treatment methods have the potential to progressively reduce the associated mortality rate over time. To diagnose sickle cell disease and its carrier states with unparalleled specificity, a variety of approaches have been developed. The most common method includes differential blood cell counts and their assessment, high-performance liquid chromatography (HPLC) and hemoglobin electrophoresis. Furthermore, innovative sensing technologies are currently under development, encompassing user-friendly, cost-effective and portable point-of-care devices that are capable of timely diagnosis at the genetic and molecular levels of these disorders. The review delves into a range of established and innovative strategies utilized in the detection of sickle cell disease, also underscoring the essential role played by diverse bio-sensing techniques in propelling the advancement of early diagnosis of SCD.

A Narrative Review of Chromatographic Bioanalytical Methods for Quantifying Everolimus in Therapeutic Drug Monitoring Applications

Background: Methods for measuring drug levels in the body are crucial for improving therapeutic drug monitoring (TDM) and personalized medicine. In solid-organ transplants, TDM is essential for the management of immunosuppressive drugs to avoid toxicity and organ rejection. Everolimus is a commonly used immunosuppressant with a small range of safe doses; therefore, it is important to adjust the dose according to each patient's needs. Therefore, reliable methods are required to accurately measure everolimus levels. This study aims to conduct a comprehensive and updated narrative review of chromatographic bioanalytical methods for everolimus quantification. Methods: The authors searched for original research articles published between 2013 and 2023 in Scopus and PubMed and found 295 articles after removing duplicates. Based on their titles and summaries, 30 articles were selected for a detailed review and 25 articles were included in the final analysis. Results: Among the 25 studies, 16 used protein precipitation, mainly with methanol, to prepare the samples, 12 used high-performance liquid chromatography, 11 used ultra-performance liquid chromatography, and 2 used both. Almost all the studies (24 of 25) used tandem mass spectrometry for detection, whereas only 1 used ultraviolet. Conclusions: This comprehensive review of bioanalytical methods for measuring everolimus using chromatography is a useful resource for researchers developing bioanalytical methods for TDM applications. Future trends in everolimus measurement include achieving lower detection limits, owing to the trend of reducing drug doses in therapy by improving sample extraction techniques and using more sensitive methods.

Assessment of amoxicillin biodegradation using a fluidized bed reactor

In recent decades, emerging pharmaceutical contaminants, such as personal care items, pharmaceuticals, and disinfectants, have increased alarmingly in aquatic ecosystems. The efficacy of wastewater treatment plants in eliminating these contaminants has been demonstrated. This study aims to find an alternative method, such as using the fluidized bed reactor (FBR) with bacteria to remove amoxicillin from wastewater. The active bacteria Acinetobacter baumannii and Klebsiella pneumoniae were isolated from one of the pharmaceutical factories in Baghdad, Iraq, from Al-Jazeera wastewater, which was used in FBR technology to decompose the antibiotic amoxicillin. The study examined several operational parameters, including pH, total organic carbon (TOC), dissolved carbon dioxide (CO2) concentration, airflow rate, amoxicillin concentration, and bacterial number, while maintaining a constant temperature. High-performance liquid chromatography (HPLC) was used to find the reaction route. The maximum amoxicillin removal efficiency was 93% and 91% for Acinetobacter baumannii and Klebsiella pneumoniae, respectively. For both bacterial species, the pH decreased due to the formation of amino acids and CO2. The suitable operation condition was 5 mg/L of amoxicillin concentration, flow rate of 30 m/s, and the number of bacteria 47 x 105 cfm/mL and 40 x 105 cfm/mL for Acinetobacter baumannii and Klebsiella pneumoniae, respectively. After treatment, the number of bacteria increased due to the degradation of amoxicillin. The steady-state time is found at 64 hours. The organic matter reaction pathway ends at the aromatic amino acid lysine, which kills gram-negative bacteria. This method was found to be successful in removing amoxicillin in low concentrations by using Acinetobacter baumannii. In the future, treating amoxicillin in wastewater using FBR technology with gram-positive bacteria is recommended.

Degradation of piroxicam and celecoxib from aqueous solution by high-energy electron beam as a Sustainable method

Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most commonly prescribed drugs that can reduce pain. This study aimed to measure the concentration of piroxicam and celecoxib in Iranian hospitals, as well as the effect of electron beam irradiation on the degradation of these pollutants in synthetic and real samples. The high-performance liquid chromatography (HPLC) was used to detect the residual analytes in the samples. The Response Surface Methodology (RSM) was used to design the experiment conditions that investigate the effect of electron beam irradiation on degradation of piroxicam and celecoxib from synthetic samples, and then according to the optimum condition, the experiments were carried out for real wastewater samples. The results of wastewater analysis shown that the mean concentration of PIRO and CELE were 6.32 ± 2.5 and 11.5 ± 3.2 μg/L, respectively. Also, the findings show that 98.98 % and 97.62 % of piroxicam and celecoxib was degraded, respectively, when the optimum conditions (pH = 4, electron beam irradiation = 8 kGy, and concentrations of 60 μg/L for piroxicam and 50 μg/L for celecoxib) were applied. Results show that the degradation rates of piroxicam and celecoxib in the real wastewater sample at optimum condition were 89.6 % and 84.25 %, respectively. So, electron beam irradiation is a long-lasting and promising method for removal emerging contaminants from wastewater, like non-steroidal anti-inflammatory drugs, that can't be removed by conventional wastewater treatment methods; so, it can be used in combination with conventional wastewater treatment methods.

Grain yellowness is an effective predictor of carotenoid content in global sorghum populations

Identification of high carotenoid germplasm is crucial to assist breeders in provitamin-A biofortification of sorghum (Sorghum bicolor [L.] Moench). High-performance liquid chromatography is the gold standard for carotenoid quantification, however, it is not feasible for large scale phenotyping due to its high cost and low throughput. In this study, we tested the feasibility of using grain color as a high-throughput method of carotenoid biofortification breeding. We hypothesized that visual, color-based selection can be an effective strategy to identify high-carotenoid accessions. Yellow grain had significantly higher carotenoid content than red, brown, and white grain. The degree of yellowness could distinguish the presence or absence of carotenoids, but could not distinguish carotenoid concentrations within yellow-only accessions. The degree of luminosity of the grain, however, was able to better predict carotenoid concentrations within yellow-only accessions. Genome-wide association studies identified significant marker-trait associations for qualitative and quantitative grain color traits and carotenoid concentrations near carotenoid pathway genes—ZEP, PDS, CYP97A, NCED, CCD, and LycE—three of which were common between grain color and carotenoid traits. These findings suggest that using grain color as a method for screening germplasm may be an effective high-throughput selection tool for prebreeding and early-stage breeding in carotenoid biofortification.

The effect of mesoporous silica doped with silver nanoparticles on glass ionomer cements; physiochemical, mechanical and ion release analysis

BackgroundThe purpose of the study was to evaluate the effect of adding mesoporous silica with silver nanoparticles to conventional glass ionomer cements (GIC) on its, physical, chemical, mechanical properties and ion release analysis.MethodsSynthesized mesoporous silica with silver nanoparticles were added in 1, 3 and 5% by weight to the liquid component of GIC forming three experimental groups and compared with plain GIC as control group. Physical and chemical characterization were conducted using nano-computerized tomography (NanoCT) and Fourier transform infrared spectroscopy. Surface microhardness, water sorption and solubility were analyzed. Ion release was investigated using Inductive Coupled Plasma-Optical Emission Spectroscopy and High Performance Liquid Chromatography. Statistical analysis between different groups for the set parameters using parametric and non-parametric tests. The results were analysed using one way analysis of variance (p < 0.05).ResultsSynthesized mesoporous silica with silver nanoparticles were of 7.28 ± 5.0 nm in diameter with a spherical morphology. NanoCT revealed less porosities for 3 wt %. Microhardness showed a statistically significant difference for 5 wt% at day 1 and 21 ( p < 0.0001). Water sorption values decreased significantly on day 14 compared to day 7 for control, 1, 3 and 5 wt%. Control specimens showed highest concentration of fluoride release followed by 5, 3 and 1 wt%.ConclusionMesoporous silica with silver nanoparticles modified glass ionomer cements showed comparable microhardness to conventional GIC. Ion release was evident from the modified specimens. Silver remained within the GIC for atleast four weeks following incorporation.

Subclinical hypothyroidism and plasma levels of commonly prescribed anti-seizure medications

Background: Epilepsy remains the most common neurological problem worldwide. Most commonly prescribed antiseizure medications (ASMs) like phenytoin, sodium valproate, and carbamazepine show high inter-individual variability in bioavailability due to genetic and epigenetic factors resulting in either therapeutic failure or toxicity. In our study, we aim to determine the association between subclinical hypothyroidism and the plasma levels of these commonly prescribed ASMs, leading to either therapeutic failure or adverse drug reactions. Methods: We collected demographic data, details about the antiepileptic medication, and plasma levels of ASMs (phenytoin, carbamazepine, and sodium valproate) from patients on antiseizure medications who came for routine therapeutic drug monitoring (TDM). High-performance liquid chromatography (HPLC) estimated plasma levels of the antiseizure medications as per the TDM laboratory standard operating procedure (SOP) and thyroid function test (TSH) by a standard enzyme-linked immune-sorbent assay (ELISA) kit. Results: Of the 158 patients who had TDM, 75.31% were taking sodium valproate, 15.18% were on phenytoin, and 9.49% were on carbamazepine monotherapy. In our study, we found that 12 patients (7.59%) had TSH levels between 4 to 10 mIU/l, indicating subclinical hypothyroidism (SCH). The plasma drug levels of all 12 patients who had SCH were found to be below the therapeutic range. Conclusions: This study has established a significant association between ASMs, particularly sodium valproate, and thyroid dysfunction, specifically SCH, in patients with epilepsy. Our findings suggest that prolonged ASM therapy can lead to thyroid disturbances, warranting careful monitoring of thyroid function in these patients.

Effect of fermentation on the constituents in the branches and leaves of Taxus media and non-small cell lung cancer

IntroductionNon-small cell lung cancer (NSCLC) is a prominent lung cancer disease worldwide. Currently, commonly used methods, such as surgery and radiotherapy, have significant side effects. Traditional Chinese medicine (TCM) has become a research hotspot because of its safe and effective characteristics. The branches and leaves of Taxus media are abundant in antitumor active compounds, and there has been no research conducted as yet regarding its anti–lung cancer molecular mechanism.ObjectiveThe aim of this study is to investigate the antitumor activity of two samples before and after fermentation of T. media, and to research the molecular mechanism of its inhibitory effect on NSCLC.MethodsThe chemical composition of pre-fermentation T. media (TM) and post-fermentation T. media qu (TMQ) were investigated using UHPLC-Q-Qrbitrap HRMS and high-performance liquid chromatography (HPLC). The anti-lung cancer activities of TM and TMQ were compared using an A549-induced tumor mouse model. An enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (H&amp;amp;E) staining, immunohistochemistry, and immunofluorescence were used to determine the of TMQ mechanism of action.ResultsThe results indicated that TM and TMQ contained 83 compounds, consisting primarily of flavonoids, organic acids, and taxanes. Both taxanes and flavonoids in TMQ were higher than that in TM. Both TM and TMQ effectively inhibited the tumor growth in non-small cell lung cancer (NSCLC), and the inhibition rate was greater in TMQ (57.24%) than in TM (49.62%). TMQ administration downregulated the tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and the glutathione (GSH) level and upregulated interferon-γ (IFN-γ), reactive oxygen species (ROS), and malondialdehyde (MDA) levels in the serum of tumor mice. TMQ treatment also increased the protein expression of Bax, Caspase-3, and Beclin-1 in tumor tissues. In contrast, the bcl-2, PI3K, Ki67, ULK1, and mTOR protein levels were suppressed by TMQ. Protein assay analyses reemphasized the superior antitumor effect of TMQ over TM. These cumulative findings demonstrated that the mechanism of action of TMQ was closely related to the activation of transcriptional misregulation in the cancer pathway that inhibited the cholinergic synaptic, AMPK, and PI3K/Akt/mTOR signaling pathways.ConclusionThis study demonstrated that fermentation increased the active ingredient contents and antitumor effects of T. media. In addition, post-fermentation TMQ was superior to TM as a herbal medicine for NSCLC treatment.