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Background/Objectives: The introduction of anti-tumor necrosis factor-α (anti-TNF-α) agents, particularly infliximab (IFX) and adalimumab (ADA), has significantly expanded the therapeutic arsenal for inflammatory bowel disease (IBD). While these biologics have demonstrated substantial efficacy, they are associated with a spectrum of potential adverse events (AEs). This study aims to evaluate and document these AEs to facilitate optimal patient selection and monitoring strategies of patients undergoing these therapies. Methods: This retrospective, single-center study examined pediatric IBD patients receiving anti-TNF-α therapy at the "Grigore Alexandrescu" Emergency Hospital for Children in Bucharest, Romania, from January 2015 to October 2024. AEs were categorized into non-infectious complications (acute infusion reactions, anti-drug antibody formation), dermatological effects (erythema nodosum, vasculitis), neurological effects (Guillain-Barré syndrome), and infections. AEs were analyzed in relation to the specific anti-TNF-α agent administered and comprehensively characterized. Results: Of 40 patients enrolled, 22 (55%) had Crohn's disease (CD). The median (IQR) age at diagnosis was 14.8 years [10.8-15.9]. IFX was used in 34 (85%) patients while 6 (15%) patients received either ADA or IFX/ADA sequential therapy. Twenty-seven AEs were documented in 19 (47.5%) patients, the most prevalent being antidrug antibody formation (44.4%), infections (22.2%), and acute infusion reactions (22.2%). All ADA-exposed patients experienced at least one AE, compared to 41.2% (n = 14) patients treated with IFX, p = 0.01. Conclusions: AEs were observed in approximately half of the study cohort, with anti-drug antibody formation emerging as the most frequent complication. ADA therapy was associated with a significantly higher rate of AEs compared to IFX. These findings underscore the critical importance of vigilant monitoring for patients undergoing anti-TNF-α therapy in pediatric IBD management.

Inappropriate and excessive use of antibiotics is responsible for the rapid development of antimicrobial resistance, which is associated with increased patient morbidity and mortality. There is an urgent need to explore new antibiotics or alternative antimicrobial agents. S. aureus a commensal microorganism but is also responsible for numerous infections. In addition to innate resistance to β-lactam antibiotics, S. aureus strains resistant to methicillin (MRSA) often show resistance to other classes of antibiotics (multidrug resistance). The advancement of phage therapy against MRSA infections offers a promising alternative in the context of increasing antibiotic resistance. Therapeutic phages are easier to obtain and cheaper to produce than antibiotics. However, there is still a lack of standards to ensure the safe use of phages, including purification, dosage, means of administration, and the quantity of phages used. Some bacteria have developed defense mechanisms against phages. The use of phage cocktails or the combination of antibiotics and phages is preferred. For personalized therapy, it is essential to set up large collections to enable phage selection. In the future, the fight against MRSA strains using phages should be based on a multidisciplinary approach, including molecular biology and medicine. Other therapies in the fight against MRSA strains include the use of endolysin antimicrobial peptides (including defensins and cathelicidins). Researchers' activities also focus on the potential use of plant extracts, honey, propolis, alkaloids, and essential oils. To date, no vaccine has been approved against S. aureus strains.

Background/objectives: This study investigates the metabolic profile of a single dose of etodolac in healthy volunteers, focusing on pharmacokinetics, clinical parameters, and metabolomic variations to identify biomarkers and pathways linked to drug response, efficacy, and safety.

Methods: Thirty-seven healthy volunteers, enrolled after rigorous health assessments, received a single dose of etodolac (Flancox^® 500 mg). Pharmacokinetic profiles were determined using tandem mass spectrometry analysis, and the metabolomic profiling was conducted using baseline samples (pre-dose) and samples at maximum drug concentration (post-dose) via liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer. Network analysis was employed to interpret the data.

Results: Correlations were observed between metabolomic profiles and pharmacokinetic parameters as well as clinical characteristics. Notably, metabolites derived from arachidonic acid, such as prostaglandins and leukotrienes, were linked to etodolac's pharmacokinetics. Other metabolites involved in pathways like cholesterol biosynthesis, bile salts, riboflavin, and retinoic acid signaling were correlated with hematological and liver function parameters. These findings are consistent with the infrequent adverse events reported by participants, including hematological and biochemical changes in liver function.

Conclusions: A set of metabolites was identified in possible associations between specific pathways and unusual side effects, comparing the metabolic profiles before and after doses of etodolac. Our results highlight the importance of optimizing drug therapy and minimizing adverse events by taking into account individual metabolic profile information.

Background: In the era of resistance, the design and search for new "small" molecules with a narrow spectrum of activity that target a protein or enzyme specific to a certain bacterium with high selectivity and minimal side effects remains an urgent problem of medicinal chemistry. In this regard, we developed and successfully implemented a strategy for the search for new hybrid molecules, namely, the not broadly known [2-(3-R-1H-[1,2,4]-triazol-5-yl)phenyl]amines. They can act as "building blocks" and allow for the introduction of certain structural motifs into the desired final products in order to enhance the antistaphylococcal effect.

Methods: The "one-pot" synthesis of the latter is based on the conversion of substituted 4-hydrazinoquinazolines or substituted 2-aminobenzonitriles and carboxylic acid derivatives to the target products. The possible molecular mechanism of the synthesized compounds (DNA gyrase inhibitors) was investigated and discussed using molecular docking, and their further study for antistaphylococcal activity was substantiated.

Results: A significant part of the obtained compounds showed high antibacterial activity against Staphylococcus aureus (MIC: 10.1-62.4 µM) and 5-bromo-2-(3-(furan-3-yl)-1H-1,2,4-triazol-5-yl)aniline and 5-fluoro-2-(3-(thiophen-3-yl)-1H-1,2,4-triazol-5-yl)aniline, with MICs of 5.2 and 6.1 µM, respectively, approaching the strength of the effect of the reference drug, "Ciprofloxacin" (MIC: 4.7 µM). The conducted SAR and ADME analyses confirm the prospects of the further structural modification of these compounds. The obtained [2-(3-R-1H-[1,2,4]-triazol-5-yl)phenyl]amines reveal significant antimicrobial activity and deserve further structural modification and detailed study as effective antistaphylococcal agents. The SAR analysis revealed that the presence of a cycloalkyl or electron-rich heterocyclic fragment in the third position of the triazole ring was essential for the antibacterial activity of the obtained compounds. At the same time, the introduction of a methyl group into the aniline moiety led to an enhancement of activity. The introduction of halogen into the aniline fragment has an ambiguous effect on the level of antistaphylococcal activity and depends on the nature of the substituent in the third position.

Conclusions: Obtained [2-(3-R-1H-[1,2,4]-triazol-5-yl)phenyl]amines reveal significant antistaphylococcal activity and deserve for further detailed study as effective antibacterial agents.

Background: Quinoa is recognized for its nutritional and pharmacological properties. This study aims to investigate the impact of salt stress induced by varying concentrations of sodium chloride (NaCl) on the production of phenolic compounds and their biological activities in different quinoa accessions. Method: Leaves from three quinoa accessions (Q4, Q24, and Q45) cultivated under increasing NaCl treatments were subjected to chemical analysis using ethanol and water extract. The concentrations of various phenolic compounds, including polyphenols, tannins, anthocyanins, and flavonoids, were quantified. HPLC-DAD-ESI-MS/MS was employed to identify the major compounds in the water extract. Additionally, antioxidants (ABTS and FRAP), anti-tyrosinase, and anti-acetylcholinesterase effects were assessed using in vitro and in silico approaches. Results: NaCl treatment significantly increased the levels of phenolic compounds across all quinoa accessions. The Q45 accession exhibited the highest accumulation of these compounds, particularly in the aqueous extracts at the 200 mM NaCl concentration. Increases were observed in flavonoids (144%), anthocyanins (125%), tannins (89%), and total polyphenols (65%) relative to controls. HPLC-DAD-ESI-MS/MS analysis corroborated these findings, showing that the main compounds also increased with higher NaCl concentrations. Furthermore, the biological efficacy tests revealed that the IC₅₀ values for both tyrosinase and acetylcholinesterase activities decreased with greater salt stress, indicating enhanced enzyme inhibition. The antioxidant activity of these extracts also showed a significant increase as the salt stress levels rose. Conclusions: Salt stress not only promotes the production of bioactive phenolic compounds in quinoa leaves but also enhances their inhibitory effects on key enzymes associated with neurodegenerative and pigmentary disorders. These findings suggest that quinoa may serve as a valuable resource for therapeutic applications, particularly under increased salinity conditions.

Background: Hepatocellular carcinoma (HCC) is the most prevalent malignant tumor, ranking fifth in terms of fatality with poor prognosis and a low survival rate. Rhoifolin (ROF), a flavonoid constituent, has previously been shown to suppress the proliferation of breast and pancreatic cancer cells. However, its inhibitory effect on HCC has remained unexplored. Objectives: Exploring the potent inhibitory activities and underlying mechanisms of ROF on HCC cells. Methods: The suppressive effect of ROF on HCC cells were assessed via CCK8 assay, apoptosis assay, cell cycle analysis and xenograft tumor mouse model. Furthermore, quantitative real-time PCR and western blot were applied to analyze the underlying mechanisms of ROF on HCC cells. Results: Firstly, the IC₅₀ values of ROF in HepG2 and HuH7 cells were 373.9 and 288.7 µg/mL at 24 h and 208.9 and 218.0 µg/mL at 48 h, respectively. Moreover, the apoptosis rates of HepG2 and HuH7 cells increased from 6.63% and 6.59% to 17.61% and 21.83% at 24 h and increased from 6.63% and 6.59% to 30.04% and 37.90% at 48 h, respectively. Additionally, ROF induced cell cycle arrest at the S phase in HCC cells. Furthermore, ROF suppressed the tumor growth of HCC cells in vivo without obvious toxicity. Mechanically, ROF facilitated apoptosis by upregulating the expression of PIDD1, CASP8, CASP9, BID, BAX, BIM, and BAK1 in HCC cells. Conclusions: ROF significantly restrains the growth of HCC cells in vitro and in vivo, which could be an effective supplement for HCC therapy.

Background/Objectives: Rapid cycle analysis (RCA) is an established and efficient methodology that has been traditionally utilized by United States health authorities to monitor post-approval vaccine safety. Initially developed in the Vaccine Safety Datalink (VSD) in early 2000s, RCA has evolved into a valuable approach for timely post-approval signal detection. Due to the availability of additional near real-time data sources and enhanced analytic approaches, the use of RCA has expanded. This narrative review provides an in-depth assessment of studies that utilized RCA for safety surveillance to detect and evaluate safety signals in post-approval vaccine monitoring. Methods: Embase and Medline were searched on 8 August 2024 to identify post-approval non-interventional vaccine safety studies using RCA or other near real-time surveillance methods published from 1 January 2018 to 31 July 2024. Data on study characteristics (e.g., study population, data source, outcomes) and RCA methodological characteristics (e.g., type of comparator, sequential testing method, confounding control method) were extracted from the eligible RCA studies. Results: Of 1128 articles screened, 18 RCA vaccine safety studies were included, of which 17 (94.4%) were conducted in the United States (US). Twelve (67%) aimed at signal detection and six (33%) conducted further signal evaluation. Over 60% examined COVID-19 vaccine safety, with half using VSD. Over 80% conducted the RCA weekly or monthly and about 78% of the studies used a database-specific historical comparator group. Conclusions: This review indicates that most of the published articles on the application of the RCA methodology in vaccine safety studies are based on research conducted in the US. With increasing availability of near real-time data sources and advanced analytic methods capabilities, RCA is expected to be more widely deployed as an active surveillance tool to complement traditional pharmacovigilance. Future studies should explore the extension of vaccine RCA methodology for non-vaccine medicinal products.

Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) are chronic, relapsing conditions characterized by dysregulated immune responses and persistent intestinal inflammation. This review aims to examine new potential therapeutic targets in IBD starting from the STRIDE-II statements. Key targets now include clinical remission, endoscopic remission, and biomarker normalization (such as C-reactive protein and fecal calprotectin). Moreover, histologic remission, transmural remission, and in the future molecular targets are emerging as important indicators of sustained disease control. The treatment goals for inflammatory bowel disease are varied: to relieve symptoms, prevent permanent intestinal damage, promote inflammation remission, and minimize complications. Consequently, the therapeutic targets have evolved to become broader and more ambitious. Integrating these advanced therapeutic targets has the potential to redefine IBD management by promoting deeper disease control and improved patient outcomes. Further research is essential to validate these strategies and optimize their clinical implementation.

Background/Objectives: Monoterpenes, a class of organic compounds with the molecular formula C₁₀H₁₆, have garnered significant attention for their potential medicinal benefits. Emerging evidence suggests they may positively influence skeletal muscle function. However, the impact of monoterpene exposure on muscle strength and mass in humans remains unclear. Methods: To explore this relationship, we analyzed data from 1202 adults (aged ≥ 18 years) who participated in the 2013-2014 National Health and Nutrition Examination Survey (NHANES), focusing on serum levels of three specific monoterpenes-α-pinene, β-pinene, and limonene-and their association with hand grip strength and lean muscle mass. Results: Our analysis revealed that, except for test 2 of hand 1, all grip strength measures showed a positive correlation with ln-limonene levels. The β coefficient for combined grip strength was 2.409 (S.E. = 0.891, p = 0.015). Positive associations were also found between serum limonene levels and lean muscle mass. The β coefficient for the Appendicular Skeletal Muscle Mass Index (ASMI) was 0.138 (S.E. = 0.041, p = 0.004). Furthermore, combined grip strength and ASMI significantly increased across limonene quintiles (p for trend = 0.005 and 0.006, respectively). However, none of the three monoterpene levels showed a significant association with clinically defined low muscle mass or low muscle strength. Conclusions: Our findings suggest a plausible association between exposure to limonene, hand grip strength, and lean muscle mass among adults in the United States. Further investigation is needed to fully understand the underlying mechanisms and medical significance of this association.

Recent developments in single-cell multi-omics technologies have provided the ability to identify diverse cell types and decipher key components of the tumor microenvironment (TME), leading to important advancements toward a much deeper understanding of how tumor microenvironment heterogeneity contributes to cancer progression and therapeutic resistance. These technologies are able to integrate data from molecular genomic, transcriptomic, proteomics, and metabolomics studies of cells at a single-cell resolution scale that give rise to the full cellular and molecular complexity in the TME. Understanding the complex and sometimes reciprocal relationships among cancer cells, CAFs, immune cells, and ECs has led to novel insights into their immense heterogeneity in functions, which can have important consequences on tumor behavior. In-depth studies have uncovered immune evasion mechanisms, including the exhaustion of T cells and metabolic reprogramming in response to hypoxia from cancer cells. Single-cell multi-omics also revealed resistance mechanisms, such as stromal cell-secreted factors and physical barriers in the extracellular matrix. Future studies examining specific metabolic pathways and targeting approaches to reduce the heterogeneity in the TME will likely lead to better outcomes with immunotherapies, drug delivery, etc., for cancer treatments. Future studies will incorporate multi-omics data, spatial relationships in tumor micro-environments, and their translation into personalized cancer therapies. This review emphasizes how single-cell multi-omics can provide insights into the cellular and molecular heterogeneity of the TME, revealing immune evasion mechanisms, metabolic reprogramming, and stromal cell influences. These insights aim to guide the development of personalized and targeted cancer therapies, highlighting the role of TME diversity in shaping tumor behavior and treatment outcomes.