BACKGROUND: The regulation of the circadian clock genes, which coordinate the activity of the immune system, is disturbed in inflammatory bowel disease (IBD). Emerging evidence suggests that butyrate, a short-chain fatty acid produced by the gut microbiota is involved in the regulation of inflammatory responses as well as circadian-clock genes. This study was conducted to investigate the effects of sodium-butyrate supplementation on the expression of circadian-clock genes, inflammation, sleep and life quality in active ulcerative colitis (UC) patients.
METHODS: In the current randomized placebo-controlled trial, 36 active UC patients were randomly divided to receive sodium-butyrate (600 mg/kg) or placebo for 12-weeks. In this study the expression of circadian clock genes (CRY1, CRY2, PER1, PER2, BMAl1 and CLOCK) were assessed by real time polymerase chain reaction (qPCR) in whole blood. Gene expression changes were presented as fold changes in expression (2^-ΔΔCT) relative to the baseline. The faecal calprotectin and serum level of high-sensitivity C-reactive protein (hs-CRP) were assessed by enzyme-linked immunosorbent assay method (ELIZA). Moreover, the sleep quality and IBD quality of life (QoL) were assessed by Pittsburgh sleep quality index (PSQI) and inflammatory bowel disease questionnaire-9 (IBDQ-9) respectively before and after the intervention.
RESULTS: The results showed that sodium-butyrate supplementation in comparison with placebo significantly decreased the level of calprotectin (-133.82 ± 155.62 vs. 51.58 ± 95.57, P-value < 0.001) and hs-CRP (-0.36 (-1.57, -0.05) vs. 0.48 (-0.09-4.77), P-value < 0.001) and upregulated the fold change expression of CRY1 (2.22 ± 1.59 vs. 0.63 ± 0.49, P-value < 0.001), CRY2 (2.15 ± 1.26 vs. 0.93 ± 0.80, P-value = 0.001), PER1 (1.86 ± 1.77 vs. 0.65 ± 0.48, P-value = 0.005), BMAL1 (1.85 ± 0.97 vs. 0.86 ± 0.63, P-value = 0.003). Also, sodium-butyrate caused an improvement in the sleep quality (PSQI score: -2.94 ± 3.50 vs. 1.16 ± 3.61, P-value < 0.001) and QoL (IBDQ-9: 17.00 ± 11.36 vs. -3.50 ± 6.87, P-value < 0.001).
CONCLUSIONS: Butyrate may be an effective adjunct treatment for active UC patients by reducing biomarkers of inflammation, upregulation of circadian-clock genes and improving sleep quality and QoL.

Colorectal cancer (CRC) represents a substantial burden on global healthcare, contributing to significant morbidity and mortality worldwide. Despite advances in screening methodologies, its incidence remains high, necessitating continued efforts in early detection and treatment. Neoplastic invasion and metastasis are primary determinants of CRC lethality, emphasizing the urgency of understanding underlying mechanisms to develop effective therapeutic strategies. This study aimed to explore the potential of serum biomarkers in predicting survival outcomes in CRC patients, with a focus on cathepsin B (CB), leukocytic elastase (LE), total sialic acid (TSA), lipid-associated sialic acid (LASA), antitrypsin activity (ATA), C-reactive protein (CRP), and cystatin C (CC). We recruited 185 CRC patients and 35 healthy controls, assessing demographic variables, tumor characteristics, and 7 serum biomarker levels, including (1) CB, (2) LE, (3) TSA, (4) LASA, (5) ATA, (6) CRP, and (7) CC. Statistical analyses included ANOVA with Tukey\'s post hoc tests and MANOVA for continuous variables. Student\'s t-test was used for dependent samples, while non-parametric tests like Mann-Whitney U and Wilcoxon signed-rank tests were applied for variables deviating from the normal distribution. Categorical variables were assessed using chi-square and Kruskal-Wallis tests. Spearman\'s rank correlation coefficient was utilized to examine variable correlations. Survival analysis employed the Kaplan-Meier method with a log-rank test for comparing survival times between groups. Significant associations were observed between CB (p = 0.04), LE (p = 0.01), and TSA (p = 0.008) levels and survival outcomes in CRC patients. Dukes\' classification stages also showed a significant correlation with survival (p = 0.001). However, no significant associations were found for LASA, ATA, CRP, and CC. Multivariate analysis of LE, TSA, and ATA demonstrated a notable correlation with survival (p = 0.041), notwithstanding ATA\'s lack of significance in univariate analysis (p = 0.13). CB, LE, and TSA emerged as promising diagnostic markers with prognostic value in CRC, potentially aiding in early diagnosis and treatment planning. Further research is needed to validate these findings and explore additional prognostic indicators.

This study aimed to investigate the effects of a single bench press (BP) vs. leg press (LP) resistance training sessions on testosterone, cortisol, C-reactive protein (CRP) interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) concentrations, and creatine kinase (CK) activity in strength-trained males. Eleven strength-trained males participated in a cross-over randomized trial, undergoing two experimental sessions each consisting of five sets of the BP or the LP exercise to volitional failure with a load corresponding to 50% of one-repetition maximum. Blood samples were taken at baseline (BA), immediately post (POST), and 1 h after the cessation of exercise (POST-1). A significant increase in IL-6 concentration from BA to POST-1 was observed during the LP condition (p = 0.004; effect size [ES] = 0.64). Additionally, a significant main effect of time was found for increasing testosterone concentrations from BA to POST exercise (p = 0.014; ES = 0.25). A significantly lower cortisol concentration at POST-1 compared to POST (p = 0.001; ES = 1.02) was noted in the BP condition. Furthermore, a significantly lower cortisol concentration was found at POST-1 in the BP compared to the LP condition (p = 0.022; ES = 1.3). A significant increase in CK activity was reported from BA to POST (p = 0.024; ES = 0.69) and POST-1 (p = 0.045; ES = 0.55) during the LP condition, and from BA to POST-1 (p = 0.014; ES = 0.96) during the BP condition. No significant differences were found in the CRP (p = 0.659) and TNF-α concentrations (p = 0.487). These results suggest that the amount of muscle mass engaged during the resistance exercise may influence the changes in IL-6 and cortisol concentrations. Larger muscle groups, as engaged in the LP, more likely lead to elevated concentrations of IL-6 myokine.

In systemic sclerosis (SSc), fibrosis of the myocardium along with ongoing autoimmune inflammation can alter the electric function of the cardiac myocytes, which may increase the risk for ventricular arrhythmias and sudden cardiac death. We analyzed the electrocardiographic (ECG) variables describing ventricular repolarization such as QT interval, QT dispersion (QTd), T wave peak-to-end interval (Tpe), and arrhythmogeneity index (AIX) of 26 patients with SSc and 36 healthy controls. Furthermore, echocardiographic and laboratory parameters were examined, with a focus on inflammatory proteins like C-reactive ptotein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), and progranulin (PGRN). The CRP, sICAM-1, and sVCAM-1 levels were positively correlated with the length of the QT interval. Although the serum PGRN levels were not increased in the SSc group compared to the controls, in SSc patients, the PGRN levels were positively correlated with the QT interval and the AIX. According to our results, we conclude that there may be a potential association between autoimmune inflammation and the risk for ventricular arrhythmias in patients with SSc. We emphasize that the measurement of laboratory parameters of inflammatory activity including CRP, PGRN, sVCAM-1, and sICAM-1 could be helpful in the prediction of sudden cardiac death in patients with SSc.

There is growing evidence that inflammation impairs erythrocyte structure and function. We assessed the impact of mild systemic inflammation on erythrocyte fragility in three different settings. In order to investigate causation, erythrocyte osmotic fragility was measured in mice challenged with a live attenuated bacterial strain to induce low-grade systemic inflammation; a significant increase in erythrocyte osmotic fragility was observed. To gather evidence that systemic inflammation is associated with erythrocyte fragility in humans, two observational studies were conducted. First, using a retrospective study design, the relationship between reticulocyte-based surrogate markers of haemolysis and high-sensitivity C-reactive protein was investigated in 9292 healthy participants of the UK Biobank project. Secondly, we prospectively assessed the relationship between systemic inflammation (measured by the urinary neopterin/creatinine ratio) and erythrocyte osmotic fragility in a mixed population (n = 54) of healthy volunteers and individuals with long-term medical conditions. Both human studies were in keeping with a relationship between inflammation and erythrocyte fragility. Taken together, we conclude that mild systemic inflammation increases erythrocyte fragility and may contribute to haemolysis. Further research is needed to assess the molecular underpinnings of this pathway and the clinical implications in inflammatory conditions.

Pre-pregnancy body mass index (pBMI) is a predictor of gestational weight gain (GWG). However, other factors, such as adipokines and inflammation markers, may also be associated with GWG. The aim of the study was to determine the association of leptin, adiponectin, irisin, and C-reactive protein, with GWG in adolescents. A longitudinal study was conducted from 2018 to 2023 in adolescents with a clinically healthy pregnancy. The assessments included sociodemographic and clinical data, pBMI, percent of body fat, serum concentrations of leptin, adiponectin, irisin, and high-sensitivity C-reactive protein (hsCRP), and total GWG adequacy. Cox regression models were performed, the outcome variables were inadequate and excessive GWG. In 198 participants, being overweight/obesity was marginally associated with a protective effect against inadequate GWG (HR = 0.44, 95%CI = 0.18-1.06), regardless of maternal characteristics and adipokines. Leptin (HR = 1.014, 95%CI = 1.008-1.021), and body fat percent (HR = 1.11, 95%CI = 1.05-1.17) were associated with a higher risk of excessive GWG, independent of other maternal variables such as pBMI, while adiponectin was associated with a lower risk. These findings suggest that, in Mexican adolescents, adipose tissue and its adipokines during pregnancy may play a more significant role in the final GWG than body weight.

The pathogenesis of anorexia nervosa (AN) has been hypothesized to involve several biological systems. However, reliable biomarkers for AN have yet to be established. This study was aimed to identify statistically significant and clinically meaningful peripheral biomarkers associated with AN. A systematic literature search was conducted to identify studies published in English from inception until 30 June 2022. We conducted two-level random-effects meta-analyses to examine the difference between AN and comparison groups across 52 distinct biomarkers and found that acylated ghrelin, adrenocorticotropic hormone (ACTH), carboxy-terminal collagen crosslinks (CTX), cholesterol, cortisol, des-acyl ghrelin, ghrelin, growth hormone (GH), obestatin, and soluble leptin receptor levels were significantly higher in cases of AN compared with those in non-AN controls. Conversely, C-reactive protein (CRP), CD3 positive, CD8, creatinine, estradiol, follicle-stimulating hormone (FSH), free thyroxine, free triiodothyronine, glucose, insulin, insulin-like growth factor 1 (IGF-1), leptin, luteinizing hormone, lymphocyte, and prolactin levels were significantly lower in AN compared with those in non-AN controls. Our findings indicate that peripheral biomarkers may be linked to the pathophysiology of AN, such as processes of adaptation to starvation. Scientific investigation into peripheral biomarkers may ultimately yield breakthroughs in personalized clinical care for AN.

High-sensitivity C-reactive protein (hs-CRP) is a widely used clinical biomarker of systemic inflammation, implicated in many chronic conditions, including type 1 diabetes (T1D). Despite the increasing emphasis on dietary intake as a modifiable risk factor for systemic inflammation, the association of hs-CRP with fruit and vegetable consumption is relatively underexplored in T1D. To address this gap, we investigated the longitudinal associations of dietary pattern-derived fruit and vegetable scores with hs-CRP in adults with and without T1D. Additionally, we examined the impact of berry consumption as a distinct food group. Data were collected in the Coronary Artery Calcification in Type 1 Diabetes study over two visits that were three years apart. At each visit, participants completed a food frequency questionnaire, and hs-CRP was measured using a particle-enhanced immunonephelometric assay. Mixed effect models were used to examine the three-year association of fruit and vegetable scores with hs-CRP. Adjusted models found a significant inverse association between blueberry intake and hs-CRP in the nondiabetic (non-DM) group. Dietary Approaches to Stop Hypertension- and Alternative Healthy Eating Index-derived vegetable scores were also inversely associated with hs-CRP in the non-DM group (all p-values ≤ 0.05). Conversely, no significant associations were observed in the T1D group. In conclusion, dietary pattern-derived vegetable scores are inversely associated with hs-CRP in non-DM adults. Nonetheless, in T1D, chronic hyperglycemia and related metabolic abnormalities may override the cardioprotective features of these food groups at habitually consumed servings.

The objective of this study is to investigate the associated risk factors and their effects on cognitive impairment (CI) in patients undergoing peritoneal dialysis. A retrospective analysis was conducted on the basic information of 268 patients who underwent continuous ambulatory peritoneal dialysis (CAPD) at our hospital from January 2020 to September 2023. Cognitive function was assessed using the Montreal Cognitive Assessment Scale during their subsequent dialysis visits. Participants were categorized into a CI group and a cognitively normal group. Blood and other biological samples were collected for relevant biomarker analysis. Subsequently, we analyzed and compared the factors influencing CI between the 2 groups. The prevalence of CI among CAPD patients was 58.2%. Compared to the cognitively normal group, the CI group had a higher prevalence of alcohol consumption, lower levels of education, and reduced serum uric acid levels (P < .05). There was also a higher incidence of autoimmune diseases such as systemic lupus erythematosus in the CI group (P < .05). In terms of dialysis efficacy, the residual kidney Kt/V and residual kidney Ccr were significantly lower in the CI group compared to the cognitively normal group. In blood parameters, the CI group showed elevated total cholesterol levels and lower serum calcium concentrations (P < .05). Logistic regression analysis identified male gender, older age, lower educational attainment, hypercholesterolemia, and elevated high-sensitivity C-reactive protein levels as independent risk factors for CI in CAPD patients (P < .05). Additionally, in this patient cohort, dialysis duration and residual renal function were protective factors against CI (P < .05). CI is prevalent among PD patients. Elevated high-sensitivity C-reactive protein levels, male gender, older age, lower educational attainment, and hypercholesterolemia constitute an independent risk factor for CI in CAPD patients, whereas residual renal function acts as a protective element.

Studies have shown that some inflammatory markers can predict the risk of cardiovascular disease (CVD) and affect the structure and function of the heart. However, a causal relationship between inflammatory markers and the cardiac structure and function has not yet been established. Thus, we conducted a 2-sample Mendelian randomization (MR) study to explore the potential causal relationship between inflammatory markers and prognostically-related left ventricular (LV) parameters. Instrumental variables (IVs) for C-reactive protein (CRP), interleukin-6 (IL-6), and myeloperoxidase (MPO) levels were selected from the databases of large genome-wide association studies (GWAS). Summary statistics for LV parameters, including LV mass, ejection fraction, end-diastolic and systolic volumes, and the ratio of LV mass to end-diastolic volume, were obtained from cardiovascular magnetic resonance studies of the UK Biobank (n = 16923). The inverse-variance weighted (IVW) method was the primary analytical method used, and was complemented with the MR-Egger, weighted median, simple mode, weighted mode, and MR pleiotropy residual sum and outlier (MR-PRESSO) methods. Sensitivity analysis was performed to evaluate the robustness of the results. CRP was significantly associated with the LV mass in the IVW method (β = -0.13 g [95% confidence interval [CI], 0.78 g-1.00 g], P = .046). A higher standard deviation of genetically-predicted CRP levels was associated with a 0.13 ± 0.06 g lower LV mass. No causal relationships of IL-6 and MPO with LV parameters were found. No evidence of heterogeneity and pleiotropy was detected. Sensitivity analyses confirmed the robustness of the results. Two-sample MR analysis revealed a causal association between increased CRP level and decreased LV mass, whereas IL-6 and MPO levels did not influence the LV parameters. However, further research is required to validate our findings.