医学最新文献

Context: Benzofuran derivatives are important structural motifs found in natural products, often exhibiting significant biological activities. Ruta graveolens L. is a plant source known for containing diverse bioactive compounds.

Objective: This study aimed to isolate and characterize compounds from the aerial parts of R. graveolens, confirm their structures through synthesis, develop a novel synthetic methodology, and evaluate their potential anti-inflammatory effects and monoamine oxidase inhibitory activity.

Materials and methods: The structures of benzofuran enantiomers were elucidated using integrated NMR, HRMS, and ECD analyses. (±)-Rutacycoumarins A and B were synthesized via a novel direct C3 alkylation of coumarin bearing phenolic hydroxyl groups. Biological evaluation assessed the anti-inflammatory effects of (±)-Rutacycoumarins A and B in LPS-stimulated HepG2 cells by measuring liver biomarkers and pro-inflammatory cytokines, and their inhibitory activity against monoamine oxidase B (MAO-B).

Results: Two novel Z/E pairs of benzofuran enantiomers, (±)-Rutacycoumarins A and B, featuring fused cyclopropane motifs, were isolated and structurally confirmed. Their synthesis employed a novel catalytic EDA complex (DIPEA/potassium ethyl xanthate donor, NHPI ester acceptor). (±)-Rutacycoumarins A and B reduced liver biomarkers and pro-inflammatory cytokines in LPS-treated HepG2 cells, and all four enantiomers inhibited MAO-B.

Conclusions: This study isolated two novel benzofuran enantiomer pairs with fused cyclopropane motifs from R. graveolens Their structures were confirmed via a new catalytic EDA complex synthesis. Racemic mixtures reduced LPS-induced liver/cellular damage and cytokines in HepG2 cells, while all enantiomers inhibited MAO-B.

The increasing prevalence of non-communicable diseases like chronic kidney disease signals the need for a deeper understanding of the impact of the intra-uterine milieu on developmental programming and its impact on health outcomes through the lifespan of an individual. Maternal health in the pre-gestational and gestational phases, including nutrition, exposure to drugs, environmental toxins, infectious and non-infectious diseases, and socio-economic conditions influence the overall development of the fetus as well as the fetal kidney. The small, vulnerable newborn, born from an adverse developmental environment, is predisposed to low nephron number and is at risk for acute kidney injury in the neonatal period. Developmental programming has far-reaching consequences, including a higher risk for cardio-kidney-metabolic diseases, including hypertension and chronic kidney disease, and pregnancy complications, which perpetuates an intergenerational cycle of non-communicable disease risk. This risk can be mitigated by optimizing the care of individuals in the reproductive age group, identifying high-risk pregnancies early, and providing optimal treatment and monitoring. Care of the small vulnerable neonate includes prevention of acute kidney injury and life-long surveillance and modulation of cardio-kidney-metabolic risk. The review focuses on highlighting the influence of maternal health in the pre-gestational and gestational phases on kidney health from the neonatal period to adulthood.

Background: The native kidney biopsy is an important diagnostic procedure in pediatric nephrology. Recent meta-analyses did not find the size of the needle as a risk factor for bleeding complications, but they were predominantly based on adult studies. There are few papers comparing the safety and core adequacy in pediatric native kidney biopsy.

Methods: We present a large single-center retrospective study performed in a tertiary pediatric nephrology center. Data of children who received a real-time ultrasound-guided native kidney biopsy with a 16- or an 18-gauge needle from 2018 to 2024 were analyzed.

Results: Overall, 1040 children (644 boys) were included, with a median age of 10.25 (6.6; 14.23) years. One hundred three (9.9%) patients experienced bleeding complications. Perinephric hematoma was reported in 86 (8.3%) cases, gross hematuria in 18 (1.7%), and 3 (0.3%) children required transfusion. Multivariate regression analysis revealed the needle size (OR for 16-gauge 2.06, 95% CI 1.22-3.47, p = 0.007) as a risk factor for complications in the overall cohort and in children under 12 years old. The needle size did not affect complication rates in children aged 12-18 years. Inadequate kidney cores were reported in 37 (4.5%) cases; OR for 18-gauge needles (OR 5.08, 95% CI 1.07-24.21, p = 0.041) was found.

Conclusions: Use of a 16-gauge needle reduces the risk of obtaining an inadequate core in comparison with an 18-gauge. An 18G needle has a safety advantage over a 16G needle in children younger than 12 years. A 16G needle is as safe as an 18G needle and should be used for native kidney biopsy in children older than 12 years.

Background: Accurate glomerular filtration rate estimation (eGFR) is essential for managing pediatric kidney transplant recipients. Given the physiology of pediatric patients receiving adult-donor kidneys, identifying the most appropriate plasma creatinine (PCr)-based formula-pediatric or adult-specific-is crucial.

Methods: This cross-sectional study included pediatric kidney transplant recipients (age 1-18 years) who received adult-donor kidneys. We compared agreement thresholds of various pediatric and adult PCr-based GFR equations with CKiD 2012 combined PCr‒cystatin C (PCr-CystC) equation via intraclass correlation coefficients (ICCs), concordance correlation coefficients (CCCs), total deviation index (TDI), P30 performance metric (P30), Bland-Altman plots, and receiver-operating characteristic (ROC) analysis. Correlation between CKiD under 25 (U25) PCr-CystC and reference CKiD 2012 equation was also evaluated.

Results: One hundred twenty samples were collected from 23 recipients (mean age = 14.2 ± 3.4 years) and donors (mean age = 31.7 ± 10.0 years). Schwartz-Lyon equation demonstrated the highest performance with the reference (ICC = 0.913, CCC = 0.911, TDI = 14.0 mL/min/1.73 m², P30 = 99.2%). U25 (ICC = 0.922, CCC = 0.882, P30 = 93.3%), full age spectrum (FAS)-height (ICC = 0.897, CCC = 0.877, P30 = 96.7%), and Bedside Schwartz equations (ICC = 0.850, CCC = 0.819, P30 = 89.2%) showed comparable performance. Bland-Altman plots revealed proportional bias (p < 0.05), leading to ROC analysis, which identified eGFR < 70 mL/min/1.73 m² for Schwartz-Lyon, U25, and FAS-height, and < 60 mL/min/1.73 m² for Bedside Schwartz as optimal agreement thresholds, beyond which each equation showed increased bias. Subgroup analyses also showed better performance in patients aged 10-18 years. Additionally, U25 PCr-CystC equation showed excellent agreement with the reference (ICC = 0.993, CCC = 0.990, P30 = 100%).

Conclusions: Schwartz-Lyon equation demonstrated the highest performance among PCr-based equations with the reference in pediatric kidney transplant recipients, particularly when eGFR was < 70 mL/min/1.73 m² and in patients aged 10-18 years. U25 PCr-CystC equation showed best overall agreement with the reference and should be preferred where CystC measurement is feasible.

Background: Measures of early postnatal fluid balance may be associated with severe intraventricular hemorrhage (sIVH) and/or death in extremely preterm infants in the first postnatal week.

Methods: A single-center, retrospective cohort study including actively treated inborn infants weighing ≥ 400 g and 22-27 weeks' gestation from 2014-2021. Longitudinal mixed effect models compared daily fluid balance covariates including serum sodium, percent weight change, total fluid intake, urine output, and fluid balance (daily weight - birth weight /birth weight × 100) among infants with and without sIVH or death, during the first seven postnatal days. Multiple regression and machine learning models were developed to predict sIVH and/or death. Variables that were incorporated into the models included measures of fluid balance, gestational age, birth weight, antenatal corticosteroids, multiples, and sex.

Results: We included 932 infants with mean ± SD gestational age of 25w2d ± 11d and birth weight of 746 ± 212 g of whom 195 (20.9%) had sIVH and/or death. Lower percentage weight change (p < 0.001), higher total fluid intake (p = 0.007), higher sodium (p = 0.007), and positive early fluid balance (p < 0.001) were associated with sIVH and/or death even after adjustment for baseline characteristics. The area under the receiver-operating curve (AUC) for regression models predicting sIVH and/or death incorporating baseline characteristics improved after adding fluid balance measures from 0.75 to 0.80, while the AUC for machine learning models improved from 0.72 to 0.84.

Conclusions: In extremely preterm infants, early fluid status measures were associated with risk of sIVH and/or death. The addition of fluid status measures improves the performance of models predicting sIVH and/or death.

Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions. The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs, which have a range of serious adverse effects. As an alternative, naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions. Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models, in the face of neuroinflammatory insults induced by lipopolysaccharide, through a systematic review and meta-analysis. A search of the preclinical literature was conducted across four databases (PubMed, Web of Science, Scielo, and Google Scholar). Studies were selected based on inclusion and exclusion criteria, assessed for methodological quality using CAMARADES, and risk of bias using the SYRCLE tool, and data were extracted from the studies. The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis. A total of 384 potentially relevant articles were identified, of which 11 studies were included in the analysis. The methodological quality was assessed, resulting in an average score of 5.8/10, and the overall risk of bias analysis revealed a lack of methodological clarity in most studies. Furthermore, through the meta-analysis, it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines, such as tumor necrosis factor alpha, interleukin 6, interleukin 1β ( n = 89; SMD = -2.00; 95% CI: -3.29 to -0.71), and microgliosis ( n = 33; SMD = -2.56; 95% CI: -4.07 to -1.10). In terms of underlying mechanisms, quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties, possibly through the nuclear factor erythroid 2-related factor 2 (Nrf2)/HO-1 pathways, increasing the expression of antioxidant enzymes and reducing reactive species, and modulating the caspase pathway, increasing levels of anti-apoptotic proteins and decreasing pro-apoptotic proteins. Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation. However, despite promising results in animal models, future directions should focus on well-designed clinical studies to assess the safety, bioavailability, and efficacy of quercetin and its derivatives in humans. Additionally, standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.

The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity, oxidative stress, inflammatory responses, and blood-brain barrier disruption. While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success, reperfusion injury remains a significant contributor to the exacerbation of brain injury. This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury. The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke, covering research progress in nanoparticle-based drug delivery, targeted therapy, and antioxidant and anti-inflammatory applications. Nano-based drug delivery systems offer several advantages compared to traditional therapies, including enhanced blood-brain barrier penetration, prolonged drug circulation time, improved drug stability, and targeted delivery. For example, inorganic nanoparticles, such as those based on CeO 2 , have been widely studied for their strong antioxidant capabilities. Biomimetic nanoparticles, such as those coated with cell membranes, have garnered significant attention owing to their excellent biocompatibility and targeting abilities. Nanoparticles can be used to deliver a wide range of neuroprotective agents, such as antioxidants (e.g., edaravone), anti-inflammatory drugs (e.g., curcumin), and neurotrophic factors. Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions. Although nanotechnology has demonstrated great potential in animal studies, its clinical application still faces several challenges, including the long-term safety of nanoparticles, the feasibility of large-scale production, quality control, and the ability to predict therapeutic effects in humans. In summary, nanotechnology holds significant promise for the treatment of ischemic stroke. Future research should focus on further exploring the mechanisms of action of nanoparticles, developing multifunctional nanoparticles, and validating their safety and efficacy through rigorous clinical trials. Moreover, interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.