The prevalence of centenarians, people who lived 100 years and longer, is steadily growing in the last decades. This exceptional longevity is based on multifaceted processes influenced by a combination of intrinsic and extrinsic factors such as sex, (epi-)genetic factors, gut microbiota, cellular metabolism, exposure to oxidative stress, immune status, cardiovascular risk factors, environmental factors, and lifestyle behavior. Epidemiologically, the incidence rate of cardiovascular diseases is reduced in healthy centenarians along with late onset of age-related diseases compared with the general aged population. Understanding the mechanisms that affect vascular ageing in centenarians and the underlying factors could offer valuable insights for developing strategies to improve overall healthy life span in the elderly. This review discusses these key factors influencing vascular ageing and how their modulation could foster healthy longevity.

• MeSH
• Longevity * physiology   MeSH
• Cardiovascular Diseases physiopathology   epidemiology   MeSH
• Humans MeSH
• Oxidative Stress physiology   MeSH
• Risk Factors MeSH
• Aged, 80 and over MeSH
• Aging * physiology   MeSH
• Gastrointestinal Microbiome physiology   MeSH
• Healthy Aging physiology   MeSH
• Life Style MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

AIMS: Liver cytochromes (CYPs) play an important role in drug metabolism but display a large interindividual variability resulting both from genetic and environmental factors. Most drug dose adjustment guidelines are based on genetics performed in healthy volunteers. However, hospitalized patients are not only more likely to be the target of new prescriptions and drug treatment modifications than healthy volunteers, but will also be more subject to polypharmacy, drug-drug interactions, or to suffer from disease or inflammation affecting CYP activities. METHODS: We compared predicted phenotype based on genetic data and measured phenotype using the Geneva cocktail to determine the extent of drug metabolizing enzyme variability in a large population of hospitalized patients (>500) and healthy young volunteers (>300). We aimed to assess the correlation between predicted and measured phenotype in the two populations. RESULTS: We found that, even in cases where the genetically predicted metabolizer group correlates well with measured CYP activity at group level, this prediction lacks accuracy for the determination of individual metabolizer capacities. Drugs can have a profound impact on CYP activity, but even after combining genetic and drug treatment information, the activity of a significant proportion of extreme metabolizers could not be explained. CONCLUSIONS: Our results support the use of measured metabolic ratios in addition to genotyping for accurate determination of individual metabolic capacities to guide personalized drug prescription.

• MeSH
• Adult MeSH
• Phenotype MeSH
• Genotype MeSH
• Hospitalization MeSH
• Pharmaceutical Preparations metabolism   MeSH
• Drug Interactions MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Aged MeSH
• Cytochrome P-450 Enzyme System * genetics   metabolism   MeSH
• Healthy Volunteers MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Heavy metals are naturally occurring components of the Earth's crust and persistent environmental pollutants. Human exposure to heavy metals occurs via various pathways, including inhalation of air/dust particles, ingesting contaminated water or soil, or through the food chain. Their bioaccumulation may lead to diverse toxic effects affecting different body tissues and organ systems. The toxicity of heavy metals depends on the properties of the given metal, dose, route, duration of exposure (acute or chronic), and extent of bioaccumulation. The detrimental impacts of heavy metals on human health are largely linked to their capacity to interfere with antioxidant defense mechanisms, primarily through their interaction with intracellular glutathione (GSH) or sulfhydryl groups (R-SH) of antioxidant enzymes such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR), and other enzyme systems. Although arsenic (As) is believed to bind directly to critical thiols, alternative hydrogen peroxide production processes have also been postulated. Heavy metals are known to interfere with signaling pathways and affect a variety of cellular processes, including cell growth, proliferation, survival, metabolism, and apoptosis. For example, cadmium can affect the BLC-2 family of proteins involved in mitochondrial death via the overexpression of antiapoptotic Bcl-2 and the suppression of proapoptotic (BAX, BAK) mechanisms, thus increasing the resistance of various cells to undergo malignant transformation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of antioxidant enzymes, the level of oxidative stress, and cellular resistance to oxidants and has been shown to act as a double-edged sword in response to arsenic-induced oxidative stress. Another mechanism of significant health threats and heavy metal (e.g., Pb) toxicity involves the substitution of essential metals (e.g., calcium (Ca), copper (Cu), and iron (Fe)) with structurally similar heavy metals (e.g., cadmium (Cd) and lead (Pb)) in the metal-binding sites of proteins. Displaced essential redox metals (copper, iron, manganese) from their natural metal-binding sites can catalyze the decomposition of hydrogen peroxide via the Fenton reaction and generate damaging ROS such as hydroxyl radicals, causing damage to lipids, proteins, and DNA. Conversely, some heavy metals, such as cadmium, can suppress the synthesis of nitric oxide radical (NO·), manifested by altered vasorelaxation and, consequently, blood pressure regulation. Pb-induced oxidative stress has been shown to be indirectly responsible for the depletion of nitric oxide due to its interaction with superoxide radical (O2·-), resulting in the formation of a potent biological oxidant, peroxynitrite (ONOO-). This review comprehensively discusses the mechanisms of heavy metal toxicity and their health effects. Aluminum (Al), cadmium (Cd), arsenic (As), mercury (Hg), lead (Pb), and chromium (Cr) and their roles in the development of gastrointestinal, pulmonary, kidney, reproductive, neurodegenerative (Alzheimer's and Parkinson's diseases), cardiovascular, and cancer (e.g. renal, lung, skin, stomach) diseases are discussed. A short account is devoted to the detoxification of heavy metals by chelation via the use of ethylenediaminetetraacetic acid (EDTA), dimercaprol (BAL), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propane sulfonic acid (DMPS), and penicillamine chelators.

• MeSH
• Antioxidants metabolism   MeSH
• Bioaccumulation MeSH
• Environmental Pollutants toxicity   MeSH
• Humans MeSH
• Oxidative Stress * drug effects   MeSH
• Metals, Heavy * toxicity   MeSH
• Environmental Exposure adverse effects   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Necrotizing enterocolitis (NEC) is one of the most devastating intestinal diseases observed in preterm in the first days of life. Researchers have recently focused on potential predictive biomarkers for early and concomitant diagnoses. Thus, we inquired about the linkage of intestinal dysbiosis, one of the most important factors in NEC development to the gut microbiota. In this study, the systematic differences in the bacterial composition between neonates affected by NEC and healthy newborns were highlighted by metagenomic analysis. The next-generation sequencing of the V3-V4 variable region of the 16S rRNA gene and gene-specific qPCR analyzed the untargeted gut microbiota. Total bacteria, total and fecal coliform loads in stool samples with NEC were higher than control. OTU-level relative abundances of NEC infant was characterized by Firmicutes and Bacteroidetes at phylum levels. At the genus level, NEC stool was identified by the lack of Klebsiella and the presence of Roseburia, Blautia, and Parasutterella. Finally, Clostridium fessum was the predominant species of Clostridium genus in disease and healthy specimens at the species level, whereas Clostridium jeddahitimonense was at NEC diagnosis. Despite a strong relationship between pathophysiology and characterization of gut microbiota at a clinical diagnosis of NEC, our results emphasize the broad difficulty in identifying potential biomarkers.

• MeSH
• Bacteria * classification   genetics   isolation & purification   MeSH
• DNA, Bacterial genetics   MeSH
• Dysbiosis microbiology   MeSH
• Feces * microbiology   MeSH
• Humans MeSH
• Metagenomics MeSH
• Enterocolitis, Necrotizing * microbiology   MeSH
• Infant, Premature MeSH
• Infant, Newborn MeSH
• RNA, Ribosomal, 16S * genetics   MeSH
• Gastrointestinal Microbiome * MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

The growth and accumulation of active ingredients of Angelica sinensis were affected by rhizosphere soil microbial communities and soil environmental factors. However, the correlationship between growth and active ingredients and soil biotic and abiotic factors is still unclear. This study explored rhizosphere soil microbial community structures, soil physicochemical properties, enzyme activities, and their effects on the growth and active ingredient contents of A. sinensis in three principal cropping areas. Results indicated that the growth indices, ligustilide, ferulic acid contents, and soil environmental factors varied in cropping areas. Pearson correlation analysis revealed that the growth of A. sinensis was affected by organic matter, total nitrogen, total phosphorus, and available phosphorus; ferulic acid and ligustilide accumulation were related to soil catalase and alkaline phosphatase activities, respectively. Illumina MiSeq sequencing showed that the genera Mortierella and Conocybe were the dominant fungal communities, and Sphingomonas, Pseudomonas, Bryobacter, and Lysobacter were the main bacterial communities associated with the rhizosphere soil. Kruskal-Wallis one-way ANOVA and Spearman correlation conjoint analysis demonstrated a significant positive correlation (p < 0.001) among the composition of the rhizosphere microbial communities at all three sampling sites. The growth and active ingredient accumulation of A. sinensis not only was significantly susceptible to the bacterial communities of Sphingomonas, Epicoccum, Marivita, Muribaculum, and Gemmatimonas but also were significantly influenced by the fungal communities of Inocybe, Septoria, Tetracladium, and Mortierella (p < 0.05). Our findings provide a scientific basis for understanding the relationship between the growth and active ingredients in A. sinensis and their corresponding rhizosphere soil microbial communities, soil physicochemical properties, and enzyme activities.

• MeSH
• Angelica sinensis * growth & development   chemistry   microbiology   MeSH
• Bacteria classification   genetics   isolation & purification   MeSH
• Nitrogen analysis   MeSH
• Phosphorus analysis   MeSH
• Fungi classification   genetics   isolation & purification   MeSH
• Microbiota * MeSH
• Soil chemistry   MeSH
• Soil Microbiology * MeSH
• Rhizosphere * MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• China MeSH

OBJECTIVES: Serum levels of uric acid (S-UA) are influenced by the interaction of genetic and environmental factors; detailed studies of hyperuricemia in children are rare. This retrospective study aimed to analyze the causes, risk factors, and therapeutic approaches associated with the development of hyperuricemia in childhood. METHODS: In a single-center study, serum uric acid levels were analyzed in 33,900 samples from 13,890 children and adolescents<19 years (6760 girls and 7130 boys) obtained between 2013 and 2023. Hyperuricemia was defined as S-UA>370μmol/L (6.22mg/dL) in girls and>420μmol/L (7.06mg/dL) in boys; mild hyperuricemia was defined as 370-420μmol/L in boys<13 years. RESULTS: In the analyzed group, hyperuricemia was found in 1753 patients (12.6%), including 586 girls and 864 boys; mild hyperuricemia was found in 303 boys<13 years. The most common associated conditions were obesity with body mass index>95th percentile (27.8% of girls, 26.3% of boys) and chronic kidney disease (18.6% of boys, 11.4% of girls). Hyperuricemia was also relatively common in children with connective tissue disorders (10.6%) or different inherited metabolic disorders (10.7%). Transitory hyperuricemia was found in 19.1% of girls and 10.1% of boys with acute gastroenteritis. Urate-lowering therapy was used in 73 children and adolescents with severe hyperuricemia (S-UA 556±107μmol/L, fraction excretion of UA 3.27±1.98%). Eight treated children had chronic kidney disease, nine were extremely obese, one had combined antiepileptic therapy, and 55 had inherited metabolic diseases, including 26 children with disorders of purine metabolism. The initial daily dose of allopurinol (50-100mg) normalized the S-UA (350±80μmol/L) in a majority of children, except for extremely obese adolescents (weight 98-149kg) where the dose had to be increased to 200-300mg. CONCLUSIONS: Asymptomatic hyperuricemia is a relatively common biochemical finding in pediatric clinical practice. The etiology of hyperuricemia should be carefully analyzed, and the value of individualized hyperuricemia management and the eventual benefits of urate-lowering therapy in children must be carefully considered.

• MeSH
• Child MeSH
• Hyperuricemia * blood   epidemiology   diagnosis   MeSH
• Infant MeSH
• Uric Acid * blood   MeSH
• Humans MeSH
• Adolescent MeSH
• Child, Preschool MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Severity of Illness Index MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Increased lung cancer risks for low socioeconomic status (SES) groups are only partially attributable to smoking habits. Little effort has been made to investigate the persistent risks related to low SES by quantification of potential biases. METHODS: Based on 12 case-control studies, including 18 centers of the international SYNERGY project (16,550 cases, 20,147 controls), we estimated controlled direct effects (CDE) of SES on lung cancer via multiple logistic regression, adjusted for age, study center, and smoking habits and stratified by sex. We conducted mediation analysis by inverse odds ratio weighting to estimate natural direct effects and natural indirect effects via smoking habits. We considered misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by genetic risk, both separately and by multiple quantitative bias analyses, using bootstrap to create 95% simulation intervals (SI). RESULTS: Mediation analysis of lung cancer risks for SES estimated mean proportions of 43% in men and 33% in women attributable to smoking. Bias analyses decreased the direct effects of SES on lung cancer, with selection bias showing the strongest reduction in lung cancer risk in the multiple bias analysis. Lung cancer risks remained increased for lower SES groups, with higher risks in men (fourth vs. first [highest] SES quartile: CDE, 1.50 [SI, 1.32, 1.69]) than women (CDE: 1.20 [SI: 1.01, 1.45]). Natural direct effects were similar to CDE, particularly in men. CONCLUSIONS: Bias adjustment lowered direct lung cancer risk estimates of lower SES groups. However, risks for low SES remained elevated, likely attributable to occupational hazards or other environmental exposures.

• MeSH
• Mediation Analysis * MeSH
• Adult MeSH
• Smoking * epidemiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Logistic Models MeSH
• Lung Neoplasms * epidemiology   MeSH
• Odds Ratio MeSH
• Risk Factors MeSH
• Aged MeSH
• Social Class * MeSH
• Case-Control Studies MeSH
• Bias * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure. METHODS: Using resources from CRC consortia, including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score, including 141 variants associated with CRC risk. RESULTS: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking (RERI = 0.24, 95% confidence interval [CI] = 0.13, 0.36), ever smoking (0.11 [0.05, 0.16]), high body mass index (female 0.09 [0.05, 0.13], male 0.10 [0.05, 0.14]), or high red meat intake (highest versus lowest quartile 0.18 [0.09, 0.27]) was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/nonsteroidal anti-inflammatory drugs use (-0.16 [-0.20, -0.11]) or higher intake of fruit, fiber, or calcium (highest quartile versus lowest quartile -0.12 [-0.18, -0.050]; -0.16 [-0.23, -0.09]; -0.11 [-0.18, -0.05], respectively) than those with average genetic susceptibility. CONCLUSIONS: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention.

• MeSH
• Diet MeSH
• Adult MeSH
• Genetic Predisposition to Disease * MeSH
• Body Mass Index MeSH
• Gene-Environment Interaction * MeSH
• Polymorphism, Single Nucleotide MeSH
• Colorectal Neoplasms * genetics   epidemiology   MeSH
• Smoking adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Logistic Models MeSH
• Alcohol Drinking MeSH
• Risk Factors MeSH
• Aged MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Eozinofilní ezofagitida je chronické zánětlivé, imunologicky podmíněné onemocnění, charakterizované patologickou infiltrací sliznice jícnu eozinofilními granulocyty. Na vzniku nemoci se podílí genetická predispozice a faktory vnějšího prostředí. Stanovení správné diagnózy se u dětí opírá o klinické příznaky dysfunkce jícnu, zvracení, neprospívání a typický histologický nález. Velmi častou komorbiditou jsou alergická onemocnění. Cílem léčby je odstranit klinické příznaky onemocnění, potlačit infiltraci jícnu eozinofilními granulocyty a zabránit komplikacím, zejména přestavbě stěny (remodelace) a zúžení jícnu. U dětí je nezbytné zajistit správný růst a vývoj. Léčba je komplexní a zahrnuje empirickou eliminační dietu nebo kombinovanou farmakoterapii inhibitorem protonové pumpy nebo topickým kortikosteroidem (budesonid jako suspenze nebo rozpustná tableta). U nejtěžších případů je indikována celková farmakoterapie prednisonem a biologická léčba (dupilumabem). Kazuistika u chlapce ukazuje na úskalí diagnostiky eozinofilní ezofagitidy v kojeneckém věku a na nutnost mezioborové spolupráce nejen při stanovení správné diagnózy a zahájení adekvátní komplexní léčby za nezbytné spolupráce rodičů nemocného dítěte, ale i při dispenzární péči a včasném rozpoznání recidivy onemocnění.

Eosinophilic esophagitis is a chronic inflammatory immune-mediated disease characterized by pathological eosinophilic infiltration of the esophageal wall. Genetic predisposition and environmental factors contribute to the development of this illnes. Establishing the correct diagnosis in children is based on clinical symptoms of esophageal dysfunction, vomiting, failure to thrive and typical histological findings. Allergic diseases are very common comorbidities. The treatment aims to remove the clinical symptoms of the disease, suppress the infiltration of the esophagus by eosinophilic granulocytes, and prevent complications, especially the remodeling of the esophagus wall with its subsequent narrowing. Ensuring proper children's growth and development is essential. Treatment of eosinophilic esophagitis is comprehensive and includes empiric elimination diet, or pharmacotherapy with proton pump inhibitors, or topical corticosteroids. In the most severe cases, systemic pharmacotherapy with prednisone and biological treatment is indicated dupilumab. The presented case report illustrates the difficulties in diagnosing in infancy and the necessity of an interdisciplinary approach (pediatrician-gastroenterologist-allergist) not only in establishing the correct diagnosis and starting adequate treatment necessitating the cooperation of the chilďs parents but also in long-term care and early recognition of the possible disease recurrence.

OBJECTIVES: To evaluate the effect of short-term inhalational exposure to nanoparticles released during dental composite grinding on oxidative stress and antioxidant capacity markers. MATERIALS AND METHODS: Twenty-four healthy volunteers were examined before and after exposure in dental workshop. They spent 76.8 ± 0.7 min in the testing room during grinding of dental nanocomposites. The individual exposure to aerosol particles in each participant ́s breathing zones was monitored using a personal nanoparticle sampler (PENS). Exhaled breath condensate (EBC), blood, and urine samples were collected pre- and post-exposure to measure one oxidative stress marker, i.e., thiobarbituric acid reactive substances (TBARS), and two biomarkers of antioxidant capacity, i.e., ferric-reducing antioxidant power (FRAP) and reduced glutathione (GSH) by spectrophotometry. Spirometry and fractional exhaled nitric oxide (FeNO) were used to evaluate the effect of acute inhalational exposure. RESULTS: Mean mass of dental nanocomposite ground away was 0.88 ± 0.32 g. Average individual doses of respirable particles and nanoparticles measured by PENS were 380 ± 150 and 3.3 ± 1.3 μg, respectively. No significant increase of the post-exposure oxidative stress marker TBARS in EBC and plasma was seen. No decrease in antioxidant capacity biomarkers FRAP and GSH in EBC post-exposure was seen, either. Post-exposure, conjunctival hyperemia was seen in 62.5% volunteers; however, no impairment in spirometry or FeNO results was observed. No correlation of any biomarker measured with individual exposure was found, however, several correlations with interfering factors (age, body mass index, hypertension, dyslipidemia, and environmental pollution parameters) were seen. CONCLUSIONS: This study, using oxidative stress biomarker and antioxidant capacity biomarkers in biological fluids of volunteers during the grinding of dental nanocomposites did not prove a negative effect of this intense short-term exposure. However, further studies are needed to evaluate oxidative stress in long-term exposure of both stomatologists and patients and diverse populations with varying health statuses.

• MeSH
• Antioxidants analysis   MeSH
• Biomarkers * analysis   MeSH
• Breath Tests MeSH
• Adult MeSH
• Glutathione analysis   MeSH
• Inhalation Exposure * adverse effects   analysis   MeSH
• Thiobarbituric Acid Reactive Substances analysis   MeSH
• Humans MeSH
• Nanocomposites * chemistry   MeSH
• Nitric Oxide analysis   metabolism   MeSH
• Oxidative Stress * MeSH
• Occupational Exposure * analysis   adverse effects   MeSH
• Dentists MeSH
• Dental Materials MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH