Effect of Single Session of Swedish Massage on Circulating Levels of Interleukin-6 and Insulin-like Growth Factor 1.

Massage therapy increases muscle blood flow and heat, relieving pain, improving immune function, and increasing vagal activity. The mechanisms are unclear. Muscles release cytokines and other peptides called myokines. These myokines exert their effects on different tissues and organs in para-, auto-, and endocrine fashion. The aim of this intervention study was to investigate if massage therapy affects circulating myokine levels. A total of 46 healthy, normal-weight subjects (15 men) aged 18-35 were recruited. Forty-five minutes of massage Swedish therapy was applied to the back and hamstrings. Blood samples via cannula were taken at the baseline, during the massage (30 min), end of the massage (45 min), and 30 min and 1 h after the massage. Interleukin 6 (IL-6) and insulin-like growth factor 1 (IGF-1) were measured as surrogate markers by ELISAs. There was a significant increase in IL-6 from 1.09 pg/mL to 1.85 pg/mL over time (Wilks' Lambda Value 0.545, p < 0.000; repeated measures ANOVA). Pair-wise comparisons showed a significant increase after 1 h of massage. No significant increase was observed in IGF-1 levels. The change in myokine levels was not correlated with muscle mass (p = 0.16, 0.74). The increase in IL-6 suggests that there might be anti-inflammatory effects, affecting glucose and lipid metabolism pathways via IL-6 signaling to muscles, fat tissue, and the liver.

Macrophage-Stimulating 1 Polymorphism rs3197999 in Pediatric Patients with Inflammatory Bowel Disease.

Background and Objectives: Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), often necessitates long-term treatment and hospitalizations and also may require surgery. The macrophage-stimulating 1 (MST1) rs3197999 polymorphism is strongly associated with the risk of IBD but its exact clinical correlates remain under investigation. We aimed to characterize the relationships between the MST1 rs3197999 genotype and the clinical characteristics in children and adolescents with IBD within a multi-center cross-sectional study. Materials and Methods: Clinical data included serum C-reactive protein (CRP), albumin, activity indices (PUCAI, PCDAI), anthropometric data, pharmacotherapy details, surgery, and disease severity. Genotyping for rs3197999 was carried out using TaqMan hydrolysis probes. Results: The study included 367 pediatric patients, 197 with Crohn's disease (CD) (40.6% female; a median age of 15.2 years [interquartile range 13.2-17.0]) and 170 with ulcerative colitis (UC) (45.8% female; a median age of 15.1 years [11.6-16.8]). No significant relationships were found between MST1 genotypes and age upon first biologic use, time from diagnosis to biological therapy introduction, PUCAI, PCDAI, or hospitalizations for IBD flares. However, in IBD, the height Z-score at the worst flare was negatively associated with the CC genotype (p = 0.016; CC: -0.4 [-1.2-0.4], CT: -0.1 [-0.7-0.8], TT: 0.0 [-1.2-0.7)]). The TT genotype was associated with higher C-reactive protein upon diagnosis (p = 0.023; CC: 4.3 mg/dL [0.7-21.8], CT 5.3 mg/dL [1.3-17.9], TT 12.2 mg/dL [3.0-32.9]). Conclusions: This study identified links between MST1 rs3197999 and the clinical characteristics of pediatric IBD: height Z-score and CRP. Further studies of the associations between genetics and the course of IBD are still warranted, with a focus on more extensive phenotyping.

Mutations in Helicobacter pylori infected patients with chronic gastritis, intestinal type of gastric cancer and familial gastric cancer.

BACKGROUND: Development of sequential changes of mucous leading to gastric cancer and familial cases of gastric cancer of intestinal type is widely connected with Helicobacter pylori infections. In this study we analysed variants of genes involved in cancerogenesis and inflammatory processes of intestines in patients infected with H.pylori. Our goal was to test whether mutations in these genes predestinate to development of gastric cancer, and whether there is a genetic factor that makes it more likely for infections with H.pylori to cause gastric cancer. As infections with H. pylori are relatively common, discovering such genetic predispositions could be used for establishing risk-groups and for planning treatments. METHODS: Our studies cover analysis of variants in genes involved in cancerogenesis: TP53 (rs11540652, rs587782329, COSM10771), MSH2 (rs193922376), MLH1 (rs63750217), and inflammatory processes of intestine: NOD2 (rs2066847, rs2066842), IL1A (rs1800587) and IL1B (rs1143634) from H.pylori-infected patients. RESULTS: Mutations were more common in the group of patients with gastric cancer of intestinal type and familial cases of gastric cancer in comparison with patients with chronic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia or gastric cancer (p-value = 0.00824), with the prevalence of p53 mutations in patients with familial gastric cancer vs. patients with other changes of mucosa (p-value = 0.000049). Additionally, gastric cancer patients have mainly genotype TT or CT of the rs2066842 variant of the NOD2 gene. CONCLUSIONS: The lack of statistically significant changes of other interleukin genes involved in inflammatory processes may suggest the presence of H.pylori infection as a potential trigger for the development of the inflammatory process of the mucosa, leading through microbiota dysbiosis to the development of enteric gastric cancer. Mutations in analysed genes correlated with more severe mucosal changes, with a much more frequent presence of TP53 gene mutations, with a limited presence of other mutations in the familial history of gastric cancer.

Vitamin K Status Based on K1, MK-4, MK-7, and Undercarboxylated Prothrombin Levels in Adolescent and Adult Patients with Cystic Fibrosis: A Cross-Sectional Study.

The available evidence on vitamin K status in cystic fibrosis (CF) is scarce, lacking data on vitamin K2 (menaquinones-MK). Therefore, we assessed vitamin K1, MK-4 and MK-7 concentrations (LC-MS/MS) in 63 pancreatic insufficient and modulator naïve CF patients, and compared to 61 healthy subjects (HS). Vitamin K1 levels did not differ between studied groups. MK-4 concentrations were higher (median <1st-3rd quartile>: 0.778 <0.589-1.086> vs. 0.349 <0.256-0.469>, p < 0.0001) and MK-7 levels lower (0.150 <0.094-0.259> vs. 0.231 <0.191-0.315>, p = 0.0007) in CF patients than in HS. MK-7 concentrations were higher in CF patients receiving K1 and MK-7 supplementation than in those receiving vitamin K1 alone or no supplementation. Moreover, vitamin K1 concentrations depended on the supplementation regime. Based on multivariate logistic regression analysis, we have found that MK-7 supplementation dose has been the only predictive factor for MK-7 levels. In conclusion, vitamin K1 levels in CF are low if not currently supplemented. MK-4 concentrations in CF patients supplemented with large doses of vitamin K1 are higher than in HS. MK-7 levels in CF subjects not receiving MK-7 supplementation, with no regard to vitamin K1 supplementation, are low. There do not seem to be any good clinical predictive factors for vitamin K status.

Pediatric endoscopy in times of pandemic: A nationwide retrospective analysis.

BACKGROUND: Gastrointestinal endoscopy is a procedure that carries an increased risk of transmission of SARS-CoV-2 infection to medical staff. In patients, COVID-19 is a risk factor for adverse events of medical procedures. This study analyzed the real-life risk of, and factors contributing to, infection transmission to endoscopic personnel, and possible adverse events of the endoscopy procedure and anesthesia in children with COVID-19. METHODS: Nationwide retrospective analysis of medical records of children with confirmed SARS-CoV-2 infection who underwent gastrointestinal endoscopy in Poland between February 2020 and February 2022. RESULTS: Fifty-eight patients were included in the analysis, 35% of whom had COVID-19 symptoms at the time of endoscopy. The dominant indications for endoscopy were foreign body or corrosive substance ingestion and gastrointestinal bleeding. Nine cases of virus transmission were registered among endoscopic personnel. In all of these cases, the endoscopy team was unaware of the patient's infection (p < 0.01), although symptoms were present in 78% of the children. Lack of use of personal protective equipment was the strongest predictor of SARS-CoV-2 transmission (p < 0.01). The risk of infection was not statistically significantly dependent on the method of anesthesia, intubation or the type of endoscopy. No statistically significant correlation was found between symptomatic infection and adverse events of endoscopy or anesthesia occurrence. There was one reported anesthesia-related adverse event involving extubation difficulties due to worsening respiratory infection symptoms. CONCLUSIONS: The risk of transmitting SARS-CoV-2 to endoscopic personnel during procedures in children is low and depends on compliance with infection prevention and control measures. Performing gastrointestinal endoscopy in children with COVID-19 does not appear to be associated with an increased risk of adverse events.

Multidirectional Effects of Red Clover (Trifolium pratense L.) in Support of Menopause Therapy.

Red clover is a raw material of interest primarily due to its isoflavone content. However, other groups of compounds may affect the pleiotropic biological effects of this raw material. It is used to alleviate menopausal symptoms, but the fact that there are many varieties of this plant that can be grown makes it necessary to compare the biological activity and phytochemical composition of this plant. Also of interest are the differences between the leaves and flowers of the plant. The aim of this study was to evaluate the properties of the leaves and flowers of six clover varieties-'Tenia', 'Atlantis', 'Milena', 'Magellan', 'Lemmon' and 'Lucrum'-with respect to their ability to inhibit α-glucosidase, lipase, collagenase and antioxidant activity. Therefore, the contents of polyphenols and the four main isoflavones-genistein, daidzein, biochanin and formononetin-were assessed. The study was complemented by testing for permeability through a model membrane system (PAMPA). Principal component analysis (PCA) identified a relationship between activity and the content of active compounds. It was concluded that antioxidant activity, inhibition of glucosidase, collagenase and lipase are not correlated with isoflavone content. A higher content of total polyphenols (TPC) was determined in the flowers of red clover while a higher content of isoflavones was determined in the leaves of almost every variety. The exception is the 'Lemmon' variety, characterized by high isoflavone content and high activity in the tests conducted.

The clinical phenotype with gastrostomy and abdominal wall infection in a pediatric patient with Takenouchi-Kosaki syndrome due to a heterozygous c.191A > G (p.Tyr64Cys) variant in CDC42: a case report.

The CDC42 (cell division cycle homolog 42) gene product, Cdc42 belongs to the Rho GTPase family which plays a pivotal role in the regulation of multiple cellular functions, including cell cycle progression, motility, migration, proliferation, transcription activation, and reactive oxygen species production. The Cdc42 molecule controls various tissue-specific functional pathways underpinning organogenesis as well as developmental integration of the hematopoietic and immune systems. Heterozygous c.191A>G (p.Tyr64Cys) pathogenic variants in CDC42 cause Takenouchi-Kosaki syndrome characterized by a spectrum of phenotypic features comprising psychomotor developmental delay, sensorineural hearing loss, growth retardation, facial dysmorphism, cardiovascular and urinary tract malformations, camptodactyly, accompanied by thrombocytopenia and immunodeficiency of variable degree. Herein, we report a pediatric patient with the Takenouchi-Kosaki syndrome due to a heterozygous p.Tyr64Cys variant in CDC42 manifesting as a congenital malformation complex accompanied by macrothrombocytopenia, poor specific antibody response, B and T cell immunodeficiency, and low serum immunoglobulin A level. We also suggst that feeding disorders, malnutrition, and a gastrointestinal infection could be a part of the phenotypic characteristics of Takenouchi-Kosaki syndrome supporting the hypothesis of immune dysregulation and systemic inflammation occurring in the p.Tyr64Cys variant in CDC42.

Methylation of RUNX3 Promoter 2 in the Whole Blood of Children with Ulcerative Colitis.

Ulcerative colitis (UC) results from a complex interplay between the environment, gut microbiota, host genetics, and immunity. Runt-related transcription factor 3 (RUNX3) regulates Th1/Th2 balance and, thus, the synthesis of cytokines and inflammation. We aimed to analyze the dependence of RUNX3 promoter 2 (P2) methylation level on: age, sex, body mass index (BMI), C-reactive protein (CRP), serum albumin, disease duration, Pediatric Ulcerative Colitis Activity Index (PUCAI), the Paris classification, and exposure to medications. This multicenter, cross-sectional study recruited hospitalized children with UC. Methylation of RUNX3 P2 was measured with methylation-sensitive restriction enzymes in the whole blood DNA. Sixty-four children were enrolled, with a mean age of 14.5 ± 2.8 years. Half of them were female (51.6%), and the average BMI Z-score was -0.44 ± 1.14. The mean methylation of RUNX3 P2 was 54.1 ± 13.3%. The methylation level of RUNX3 P2 did not correlate with age, sex, nutritional status, CRP, albumin, PUCAI, or the extent of colitis (Paris E1-E4). RUNX3 P2 methylation did not differ between patients recruited within two and a half months of diagnosis and children who had UC for at least a year. Current or past exposure to biologics, immunosuppressants, or steroids was not associated with RUNX3 P2 methylation. Methylation of RUNX3 promoter 2 in whole blood DNA does not seem to be associated with the characteristics of UC in children.

C-Reactive Protein/Albumin Ratio at Diagnosis of Pediatric Inflammatory Bowel Disease: A Retrospective Multi-Center Study.

BACKGROUND This study aimed to evaluate the C-reactive protein-to-albumin (CRP/albumin) ratio at diagnosis of pediatric inflammatory bowel disease (IBD). MATERIAL AND METHODS Serum CRP/albumin ratio was calculated for patients with Crohn's disease (CD; n=186) and ulcerative colitis (UC; n=159) aged 3-18 years. RESULTS Patients with CD differed in CRP/albumin ratio at diagnosis in groups with quiescent, mild, moderate, and severe disease (P=0.011). CRP/albumin ratio at diagnosis was significant in differentiating patients with severe CD from quiescent disease at diagnosis (area under the curve (AUC)=0.94, odds ratio (OR)=63.4, 95% confidence interval (CI) 7.1-569.1, P<0.0001). CRP/albumin ratio at diagnosis could moderately differentiate penetrating from non-penetrating disease behavior in CD at diagnosis (AUC=0.73, OR=6.3, 95% CI 2.0-19.3, P<0.001). Furthermore, CRP/albumin ratio at diagnosis weakly differentiated IBD patients in need of biological treatment in a step-up procedure (AUC=0.58, OR=2.1, 95% CI 1.3-3.4, P=0.022) and in need of surgery (AUC=0.63, OR=3.1, 95% CI 1.4-7.2, P=0.006). For the IBD, CRP/albumin ratio at diagnosis was weakly correlated with age at first immunosuppressive treatment (rho=0.20, P=0.018), time from diagnosis to first biological treatment (rho=-0.37, P<0.001), days spent in hospital (rho=0.26, P=0.007), number of severe relapses (rho=0.31, P=0.001), and Pediatric Crohn's Disease Activity Index (rho=0.38, P=0.002). CONCLUSIONS The present findings add to previous studies carried out in adult patients and show that the CRP/albumin ratio at diagnosis was not significantly associated with the course of either CD or UC in children. However, CRP/albumin ratio could differentiate patients with severe CD from those with quiescent disease.

The Dark Side of Iron: The Relationship between Iron, Inflammation and Gut Microbiota in Selected Diseases Associated with Iron Deficiency Anaemia-A Narrative Review.

Iron is an indispensable nutrient for life. A lack of it leads to iron deficiency anaemia (IDA), which currently affects about 1.2 billion people worldwide. The primary means of IDA treatment is oral or parenteral iron supplementation. This can be burdened with numerous side effects such as oxidative stress, systemic and local-intestinal inflammation, dysbiosis, carcinogenic processes and gastrointestinal adverse events. Therefore, this review aimed to provide insight into the physiological mechanisms of iron management and investigate the state of knowledge of the relationship between iron supplementation, inflammatory status and changes in gut microbiota milieu in diseases typically complicated with IDA and considered as having an inflammatory background such as in inflammatory bowel disease, colorectal cancer or obesity. Understanding the precise mechanisms critical to iron metabolism and the awareness of serious adverse effects associated with iron supplementation may lead to the provision of better IDA treatment. Well-planned research, specific to each patient category and disease, is needed to find measures and methods to optimise iron treatment and reduce adverse effects.

Sodium Butyrate Effectiveness in Children and Adolescents with Newly Diagnosed Inflammatory Bowel Diseases-Randomized Placebo-Controlled Multicenter Trial.

BACKGROUND: Butyric acid's effectiveness has not yet been assessed in the pediatric inflammatory bowel disease (IBD) population. This study aimed to evaluate the effectiveness of oral sodium butyrate as an add-on to standard therapy in children and adolescents with newly diagnosed IBD. METHODS: This was a prospective, randomized, placebo-controlled multicenter study. Patients aged 6-18 years with colonic Crohn's disease or ulcerative colitis, who received standard therapy depending on the disease's severity, were randomized to receive 150 mg sodium butyrate twice a day (group A) or placebo (group B). The primary outcome was the difference in disease activity and fecal calprotectin concentration between the two study groups measured at 12 weeks of the study. RESULTS: In total, 72 patients with initially active disease completed the study, 29 patients in group A and 43 in group B. At week 12 of the study, the majority of patients achieved remission. No difference in remission rate or median disease activity was found between the two groups (p = 0.37 and 0.31, respectively). None of the patients reported adverse events. CONCLUSIONS: A 12-week supplementation with sodium butyrate, as adjunctive therapy, did not show efficacy in newly diagnosed children and adolescents with IBD.

Bioavailability of Hesperidin and Its Aglycone Hesperetin-Compounds Found in Citrus Fruits as a Parameter Conditioning the Pro-Health Potential (Neuroprotective and Antidiabetic Activity)-Mini-Review.

Hesperidin and hesperetin are polyphenols that can be found predominantly in citrus fruits. They possess a variety of pharmacological properties such as neuroprotective and antidiabetic activity. However, the bioavailability of these compounds is limited due to low solubility and restricts their use as pro-healthy agents. This paper described the limitations resulting from the low bioavailability of the presented compounds and gathered the methods aiming at its improvement. Moreover, this work reviewed studies providing pieces of evidence for neuroprotective and antidiabetic properties of hesperidin and hesperetin as well as providing a detailed look into the significance of reported modes of action in chronic diseases. On account of a well-documented pro-healthy activity, it is important to look for ways to overcome the problem of poor bioavailability.

Comparison of the Effect of Endurance, Strength, and Endurance-Strength Training on Inflammatory Markers and Adipokines Levels in Overweight and Obese Adults: Systematic Review and Meta-Analysis of Randomised Trials.

The aim of this meta-analysis was to compare the effects of endurance, strength, and combined training on inflammatory markers and adipokine concentrations in overweight and obese adults. We performed a literature search of the Cochrane Library, PubMed, Scopus, and Web of Science databases and identified 24 randomised control trials published prior to June 2021. Our findings indicate that endurance training was significantly more beneficial than strength training in reducing C-reactive protein (CRP) (standard mean difference (SMD): -1.317, 95% confidence intervals (CI): -2.565, -0.070, p = 0.0385), interleukin 6 (IL-6) (SMD: -0.363, 95% CI: -0.648, -0.078, p = 0.0126), and visfatin (SMD: -0.618, 95% CI: -1.015, -0.222, p = 0.0023) concentrations. Moreover, combined training was more beneficial than strength training alone in lowering tumour necrosis factor-alpha (TNF-α) levels (SMD: 0.890, 95% CI: -0.301, 1.478, p = 0.0030). There were no differences between the effects of different types of training programmes on adiponectin and leptin concentrations. In conclusion, compared with strength training, endurance training is more effective in lowering CRP, IL-6, and visfatin concentrations, while combined training is more beneficial in reducing TNF-α levels in overweight and obese adults. Further studies are needed to determine which type of training has a better effect on adiponectin and leptin concentrations in this population.

Differential correlation network analysis of rectal transcriptomes reveals cystic fibrosis-related disturbance.

Background: Intestinal pathology in cystic fibrosis (CF) remains mechanistically underexplored. Aim: We hypothesized that differential correlation network analysis of expression data would reveal hub genes of CF-related disturbance in the large bowel. Materials & methods: Transcriptomes of 29 rectal tissue samples were accessed at ArrayExpress (E-GEOD-15568 by Stanke et al.). Results: We identified 279 transcript pairs differentially correlating in CF and controls, including: ESRRA and RPL18 (rCF = 0.55; rcontrols = -0.68; padj = 1.60 × 10-100), SRP14 and FAU (rCF = -0.69; rcontrols = 0.48; padj = 2.99 × 10-90), SRP14 and GDI2 (rCF = -0.34; rcontrols = 0.60; padj = 1.05 × 10-78). The genes related to membrane protein targeting (q = 8.34 × 10-14) and one cluster was clearly linked to male infertility. Conclusion:FAU, SRP14 and GDI2 may be involved in a compensatory protein trafficking mechanism in CF rectum, highlighting their potential therapeutic value.

Characterisation of the Circulating Transcriptomic Landscape in Inflammatory Bowel Disease Provides Evidence for Dysregulation of Multiple Transcription Factors Including NFE2, SPI1, CEBPB, and IRF2.

AIM: To assess the pathobiological and translational importance of whole-blood transcriptomic analysis in inflammatory bowel disease [IBD]. METHODS: We analysed whole-blood expression profiles from paired-end sequencing in a discovery cohort of 590 Europeans recruited across six countries in the IBD Character initiative (newly diagnosed patients with Crohn's disease [CD; n = 156], ulcerative colitis [UC; n = 167], and controls [n = 267]), exploring differential expression [DESeq2], co-expression networks [WGCNA], and transcription factor involvement [EPEE, ChEA, DoRothEA]. Findings were validated by analysis of an independent replication cohort [99 CD, 100 UC, 95 controls]. In the discovery cohort, we also defined baseline expression correlates of future treatment escalation using cross-validated elastic-net and random forest modelling, along with a pragmatic ratio detection procedure. RESULTS: Disease-specific transcriptomes were defined in IBD [8697 transcripts], CD [7152], and UC [8521], with the most highly significant changes in single genes, including CD177 (log2-fold change [LFC] = 4.63, p = 4.05 × 10-118), MCEMP1 [LFC = 2.45, p = 7.37 × 10-109], and S100A12 [LFC = 2.31, p = 2.15 × 10-93]. Significantly over-represented pathways included IL-1 [p = 1.58 × 10-11], IL-4, and IL-13 [p = 8.96 × 10-9]. Highly concordant results were obtained using multiple regulatory activity inference tools applied to the discovery and replication cohorts. These analyses demonstrated central roles in IBD for the transcription factors NFE2, SPI1 [PU.1], CEBPB, and IRF2, all regulators of cytokine signalling, based on a consistent signal across cohorts and transcription factor ranking methods. A number of simple transcriptome-based models were associated with the need for treatment escalation, including the binary CLEC5A/CDH2 expression ratio in UC (hazard ratio = 23.4, 95% confidence interval [CI] 5.3-102.0). CONCLUSIONS: Transcriptomic analysis has allowed for a detailed characterisation of IBD pathobiology, with important potential translational implications.

Fat-Soluble Vitamins in Standard vs. Liposomal Form Enriched with Vitamin K2 in Cystic Fibrosis: A Randomized Multi-Center Trial.

BACKGROUND: We aimed to assess a liposomal fat-soluble vitamin formulation containing vitamin K2 with standard treatment in cystic fibrosis (CF). METHODS: A multi-center randomized controlled trial was carried out in 100 pancreatic-insufficient patients with CF. The liposomal formulation contained vitamin A as retinyl palmitate (2667 IU daily) and beta-carotene (1333 IU), D3 (4000 IU), E (150 IU), K1 (2 mg), and K2 as menaquinone-7 (400 µg). It was compared with the standard vitamin preparations in the closest possible doses (2500 IU, 1428 IU, 4000 IU, 150 IU, 2.14 mg, respectively; no vitamin K2) over 3 months. RESULTS: Forty-two patients finished the trial in the liposomal and 49 in the control group (overall 91 pts: 22.6 ± 7.6 years, 62.6% female, BMI 19.9 ± 2.8 kg/m2, FEV1% 70% ± 30%). The main outcome was the change of vitamin status in the serum during the study (liposomal vs. standard): all-trans-retinol (+1.48 ± 95.9 vs. -43.1 ± 121.4 ng/mL, p = 0.054), 25-hydroxyvitamin D3 (+9.7 ± 13.4 vs. +2.0 ± 9.8 ng/mL, p = 0.004), α-tocopherol (+1.5 ± 2.5 vs. -0.2 ± 1.6 µg/mL, p < 0.001), %undercarboxylated osteocalcin (-17.2 ± 24.8% vs. -8.3 ± 18.5%, p = 0.061). The secondary outcome was the vitamin status at the trial end: all-trans-retinol (370.0 ± 116.5 vs. 323.1 ± 100.6 ng/mL, p = 0.045), 25-hydroxyvitamin D3 (43.2 ± 16.6 vs. 32.7 ± 11.5 ng/mL, p < 0.001), α-tocopherol (9.0 ± 3.1 vs. 7.7 ± 3.0 µg/mL, p = 0.037), %undercarboxylated osteocalcin (13.0 ± 11.2% vs. 22.7 ± 22.0%, p = 0.008). CONCLUSION: The liposomal fat-soluble vitamin supplement containing vitamin K2 was superior to the standard form in delivering vitamin D3 and E in pancreatic-insufficient patients with CF. The supplement was also more effective in strengthening vitamin K-dependent carboxylation, and could improve vitamin A status.

Immune cell-specific smoking-related expression characteristics are revealed by re-analysis of transcriptomes from the CEDAR cohort.

Introduction: Smoking is known to affect whole-blood expression and methylation profiles. Although whole-genome methylation studies indicated that effects observed in blood may be driven by changes within leukocyte subtypes, these phenomena have not been explored using expression profiling. Material and methods: This study reanalyzed data from the Correlated Expression and Disease Association Research (CEDAR) patient cohort recruited by Momozawa et al. (E-MTAB-6667). Data from gene expression profiling of immunomagnetically sorted CD4+, CD8+, CD14+, CD15+, and CD19+ cells were processed. Differential expression analyses were conducted in each immune cell type, followed by gene ontology analysis and supplementary investigations. Results: Ninety-four differentially expressed genes were found (CD8+ n = 58, CD14+ n = 20, CD4+ n = 14, CD19+ n = 2). Two key smoking-related genes were overexpressed in specific cell types: LRRN3 (CD4+, CD8+) and MMP25 (CD8+, CD14+). In CD4+ cells smoking was associated with reduced expression of the NK cell receptor KLRB1, suggesting CD4+ subpopulation shifts and differences in interferon signaling (reduced IRF1 and IL18RAP in smokers). Key results and their integration with an immune protein-protein interaction network revealed that smoking influences integrins in CD8+ cells (ITGB7, ITGAL, ITGAM, ITGB2). C-type lectin CLEC4A was reduced in CD8+ cells and CLEC10A was increased in CD14+ cells from smokers; moreover, CLEC5A (CD8+), CLEC7A (CD8+) and CLEC9A (CD19+) were related to smoking in supplementary analyses. CD14+ cells from smokers exhibited overexpression of LDLR and the formyl peptide receptor FPR3. Conclusions: Smoking specifically alters vital immune regulation genes in lymphocyte subtypes, especially CD4+, CD8+ and CD14+ cells.

The Relationship between Eosinophil Density in the Colonic Mucosa and Eosinophil Blood Count in Children: A Cross-Sectional Study.

Eosinophils are found in the mucosa of the healthy gastrointestinal tract, but they also often accompany gastrointestinal diseases. We hypothesized that a positive correlation exists between blood eosinophil count and colonic eosinophil mucosal density in children. Electronic health records regarding 181 colonoscopies, performed with biopsy in the years 2019-2022, were screened for information on blood and colonic eosinophil count, age, sex, diagnoses, weight, height, white blood cell (WBC) count, serum C-reactive protein (CRP), and total IgE concentration. The median age (IQR) of the 107 included children (109 colonoscopies) was 12.4 years (8.1-15.5); 32 presented with blood eosinophilia (29.3%). The median eosinophil density/high-power field in the colonic mucosa was 22.5 (9-31). We found a weak correlation between colonic mucosal eosinophil density and blood eosinophil count (r = 0.295, 95% CI 0.108-0.462, p = 0.0018). This association was more pronounced in patients with elevated CRP (r = 0.529, 95% CI 0.167-0.766, p = 0.0054) and older than 12.4 years (r = 0.448, 95% CI 0.197-0.644, p = 0.00068). Peripheral blood eosinophilia might hint at increased mucosal colonic eosinophil density, especially in older children and in the presence of systemic inflammation. However, it seems unlikely that blood and colonic eosinophilia are strongly linked in younger children. Studies in adults are warranted.

Serum bile acids in cystic fibrosis patients - glycodeoxycholic acid as a potential marker of liver disease.

BACKGROUND: Cystic fibrosis (CF) and CF-related liver disease can lead to disturbances in bile acid metabolism. AIM: This study determined serum bile acid concentrations in CF to define their usefulness in liver disease assessment. METHODS: Primary, secondary and conjugated bile acid levels were measured in three CF groups (25 patients each) exhibiting: liver cirrhosis, other liver disease, no liver disease, and in 25 healthy subjects (HS). RESULTS: Bile acid levels were higher in CF patients than in HS, except for glycodeoxycholic acid (GDCA). However, bile acid concentrations did not differ between patients with cirrhosis and other liver involvement. GDCA and deoxycholic acid (DCA) differentiated CF patients with non-cirrhotic liver disease from those without liver disease (GDCA-AUC: 0.924, 95%CI 0.822-1.000, p<0.001; DCA-AUC: 0.867, 95%CI: 0.731-1.000, p<0.001). Principal component analysis revealed that in CF liver disease was related to GDCA, GGTP activity, severe genotype and pancreatic insufficiency. CONCLUSIONS: A CF-specific bile acid profile was defined and shown to relate to liver disease. GDCA differentiates patients with non-cirrhotic liver involvement from those with no detectable liver disease. Hence, GDCA is a candidate for validation as a biomarker of non-cirrhotic progression of liver disease in CF.