Search

The ultrasound-assisted extraction technique was used for extracting polysaccharides of Tricholoma matsutake (PTM) in this work. The effects of different parameters, i.e., solid-to-liquid ratio, ultrasonic power, extraction time, and extraction temperature on the PTM yield were optimized using a rotatable, orthogonal central composite design. In the derived optimal conditions, the PTM yield was 16.97 ± 0.06%, which corresponded well with the regression model predicted value of 16.85%. The extracted PTM was purified, and the structural characteristics and antioxidant activities were investigated. The PTM was found to be composed mainly of fructose, mannose, glucose, and galactose with a molar molecular ratio of 1:2.25:9.35:5, and an average molecular weight of 90,100 Da. High antioxidant effects of PTM were seen in the tests of DPPH, hydroxyl, and ABTS radical scavenging, along with a moderate superoxide radical scavenging rate. [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: Non‐selective beta‐blockers (NSBB) are a well‐established treatment in patients with clinically significant portal hypertension. However, their potential role after insertion of a transjugular intrahepatic portosystemic shunt (TIPS) still needs to be determined. Of note, recent studies suggested that favourable anti‐inflammatory effects of NSBB might be independent from pressure reduction. This study aimed to evaluate whether NSBB‐treatment is associated with amelioration of systemic inflammation (SI), hepatic decompensation and survival after TIPS‐insertion. Methods: In a retrospective study comprising 305 consecutive patients, we investigated the impact of NSBB‐intake at TIPS‐placement on periinterventional cirrhosis‐associated complications and continued NSBB‐treatment after discharge on complications including hepatic decompensation and mortality during 1‐year follow‐up, employing multivariable competing‐risk‐analyses. In a prospective cohort including 45 patients, we performed a comprehensive analysis of SI analysing 48 soluble inflammatory markers (SIMs) at baseline plus 3 and 6 months after TIPS‐insertion. Results: Overall, 175 (57.4%) patients received NSBB‐therapy prior to TIPS‐insertion; upon discharge, this decreased to 131 (22.9%), with 36 (27.5%) discontinuing NSBB within 1‐year follow‐up. Neither NSBB‐therapy at TIPS‐insertion nor treatment‐continuation after discharge were associated with lower risks for hepatic decompensation, individual cirrhosis‐associated complications or mortality neither in the periinterventional period nor during follow‐up. Similarly, in the prospective cohort NSBB‐intake was not linked to lower levels or a more prominent change of WBC, CRP or any other SIM at any of the investigated time points. Conclusion: NSBB‐therapy at the time of TIPS‐insertion and its (dis‐)continuation afterwards seems to have no significant impact on SI, development of hepatic decompensation and survival. [ABSTRACT FROM AUTHOR]

Bacillus Calmette–Guérin vaccine is well known for inducing trained immunity in myeloid and natural killer cells, which can explain its cross-protective effect against heterologous infections. Although displaying functional characteristics of both adaptive and innate immunity, γδ T-cell memory has been only addressed in a pathogen-specific context. In this study, we aimed to determine whether human γδ T cells can mount trained immunity and therefore contribute to the cross-protective effect of the Bacillus Calmette–Guérin vaccine. We investigated in vivo induction of innate memory in γδ T cells by Bacillus Calmette–Guérin vaccination in healthy human volunteers by combining single-cell RNA sequencing technology with immune functional assays. The total number of γδ T cells and membrane markers of activation was not influenced by Bacillus Calmette–Guérin vaccination. In contrast, Bacillus Calmette–Guérin changed γδ T cells' transcriptional programs and increased their responsiveness to heterologous bacterial and fungal stimuli, including lipopolysaccharide and Candida albicans , as simultaneously characterized by higher tumor necrosis factor and interferon γ production, weeks after vaccination. Human γδ T cells in adults display the potential to develop a trained immunity phenotype after Bacillus Calmette–Guérin vaccination. [ABSTRACT FROM AUTHOR]

Background and Aims: Systemic Inflammation (SI) is considered a key mechanism in disease progression and development of complications in decompensated liver cirrhosis. SI is mainly driven by portal hypertension and bacterial translocation. Transjugular intrahepatic portosystemic shunt (TIPS)-insertion represents an effective treatment for portal hypertension. This study aims to investigate the impact of TIPS-insertion on SI and bacterial translocation., Methods: We prospectively included 59 cirrhotic patients undergoing TIPS-insertion. Blood samples were collected at TIPS-insertion and follow-up 1, 3, 6, and 12 months (FU) thereafter. At all time points, we performed a comprehensive analysis of SI including 43 soluble inflammatory markers (SIMs), and surrogates of bacterial translocation (sCD14, sCD163). To investigate long-term kinetics of SI, C-reactive protein (CRP) and white blood cells (WBC) were retrospectively analyzed in a cohort of 177 patients up to 3-years after TIPS-insertion., Results: At TIPS-insertion, 30/43 SIMs, sCD14, and sCD163 measured significantly higher in cirrhotic patients compared to healthy controls. By FU6 25 SIMs and sCD14 measured at significantly lower levels compared to baseline. Interestingly, in patients with TIPS-indication refractory ascites IL-6 decreased to levels documented in earlier stages of cirrhosis. In long-term follow-up, CRP-levels significantly decreased after TIPS-insertion, which translated into improved liver-transplant-free survival in cox regression analysis (HR 0.968, p=0.042). Notably, patients with residual ascites post-TIPS showed significantly higher CRP- and IL-6 levels across all follow-ups compared to patients with resolved ascites., Conclusions: Decreasing portal hypertension via TIPS-insertion leads to a significant attenuation of SI and bacterial translocation over time.

Vaccination-induced protection against influenza is greatly diminished and increasingly heterogeneous with age. We investigated longitudinally (up to five time points) a cohort of 234 vaccinated >65-year-old vaccinees with adjuvanted vaccine FluAd across two independent seasons. System-level analyses of multiomics datasets measuring six modalities and serological data revealed that poor responders lacked time-dependent changes in response to vaccination as observed in responders, suggestive of systemic dysregulation in poor responders. Multiomics integration revealed key molecules and their likely role in vaccination response. High prevaccination plasma interleukin-15 (IL-15) concentrations negatively associated with antibody production, further supported by experimental validation in mice revealing an IL-15-driven natural killer cell axis explaining the suppressive role in vaccine-induced antibody production as observed in poor responders. We propose a subset of long-chain fatty acids as modulators of persistent inflammation in poor responders. Our findings provide a potential link between low-grade chronic inflammation and poor vaccination response and open avenues for possible pharmacological interventions to enhance vaccine responses.

Background: Urate concentration and the physiological regulation of urate homeostasis exhibit clear sex differences. DNA methylation has been shown to explain a substantial proportion of serum urate variance, mediate the genetic effect on urate concentration, and co-regulate with cardiometabolic traits. However, whether urate concentration is associated with DNA methylation in a sex-dependent manner is unknown. Additionally, it is worth investigating if urate changes after perturbations, such as vaccination, are associated with DNA methylation in a sex-specific manner., Methods: We investigated the association between DNA methylation and serum urate concentrations in a Dutch cohort of 325 healthy individuals. Urate concentration and DNA methylation were measured before and after Bacillus Calmette-Guérin (BCG) vaccination, used as a perturbation associated with increased gout flares. The association analysis included united, interaction, and sex-stratified analysis. Validation of the identified CpG sites was conducted using three independent cohorts., Results: 215 CpG sites were associated with serum urate in males, while 5 CpG sites were associated with serum urate in females, indicating sex-specific associations. Circulating urate concentrations significantly increased after BCG vaccination, and baseline DNA methylation was associated with differences in urate concentration before and after vaccination in a sex-specific manner. The CpG sites associated with urate concentration in males were enriched in neuro-protection pathways, whereas in females, the urate change-associated CpG sites were related to lipid and glucose metabolism., Conclusion: Our study enhances the understanding of how epigenetic factors contribute to regulating serum urate levels in a sex-specific manner. These insights have significant implications for the diagnosis, prevention, and treatment of various urate-related diseases and highlight the importance of personalized and sex-specific approaches in medicine., Competing Interests: Additional Declarations: There is NO Competing Interest.