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Chronic liver diseases (CLD) affect 1.5 billion patients worldwide, with dramatically increasing incidence in recent decades. It has been hypothesized that the chronic hyperinflammation associated with CLD may increase the risk of a more severe course of acute pancreatitis (AP). This study aims to investigate the underlying impact of CLD on the outcomes of AP. A systematic search was conducted in Embase, Medline, and Central databases until October 2022. Studies investigating patients with acute pancreatitis and CLD, were included in the meta-analysis. A total of 14,963 articles were screened, of which 36 were eligible to be included. CLD was a risk factor for increased mortality with an odds ratio (OR) of 2.53 (CI 1.30 to 4.93, p  = 0.01). Furthermore, renal, cardiac, and respiratory failures were more common in the CLD group, with ORs of 1.92 (CI 1.3 to 2.83, p  = 0.01), 2.11 (CI 0.93 to 4.77, p  = 0.062) and 1.99 (CI 1.08 to 3.65, p  = 0.033), respectively. Moreover, the likelihood of developing Systemic Inflammatory Response Syndrome (SIRS) was significantly higher, with an OR of 1.95 (CI 1.03 to 3.68, p  = 0.042). CLD is an important risk factor for worse outcomes in AP pancreatitis, leading to higher mortality and increased rates of local and systemic complications.

Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is a biliary drainage technique performed in endoscopic centers worldwide. No consensus exists on the different types of stents used. This study assessed the efficacy and safety profile of different EUS-HGS stents in malignant biliary obstruction. This systematic review and meta-analysis followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (2020) guidelines. Three databases were searched for studies on HGS with plastic or metallic stents from inception to February 5, 2025. Primary outcomes were clinical success, overall adverse events with and without biliary obstruction, and recurrent biliary obstruction (RBO). A random-effects model was used to calculate pooled odds ratios (OR), hazard ratios (HR), and proportion rates with 95% confidence intervals (CIs). A total of 25 studies were included. Adverse events excluding RBO were significantly less with plastic stents (OR: 2.20, CI: 1.26-3.84), while the risk of RBO was higher compared to metallic stents (HR: 1.60, CI: 1.21-2.12). There was no significant difference in clinical success between plastic and metallic stents (OR: 0.96, CI: 0.28-3.26). The pooled clinical success rates were 92% (CI: 87%-95%) for plastic stents, 89% (CI: 82%-94%) for partially covered self-expandable metal stents (PCSEMS), 96% (CI: 87%-99%) for fully covered SEMS, and 92% (CI: 86%-95%) for PCSEMS with anchoring. Metallic stents have a longer-term patency than plastic stents. Overall, adverse events were less common with plastic stents, and the clinical success was not different. Therefore, patients with short life expectancy may not benefit from metallic stent use in EUS-HGS. This study was registered with the following number. PROSPERO: CRD42024509412.

The multi-domain muscle protein titin provides elasticity and mechanosensing functions to the sarcomere. Titin’s PEVK domain is intrinsically disordered due to the presence of a large number of prolines and highly charged residues. Although PEVK does not have canonical actin-binding motifs, it has been shown to bind F-actin. Here, we explored whether the PEVK domain may also affect actin assembly. We cloned the middle, 733-residue-long segment (called PEVKII) of the full-length PEVK domain, expressed in E. coli and purified by using His- and Avi-tags engineered to the N- and C-termini, respectively. Actin assembly was monitored by the pyrene assay in the presence of varying PEVKII concentrations. The structural features of PEVKII-associated F-actin were studied with atomic force microscopy. The added PEVKII enhanced the initial and log-phase rates of actin assembly and the peak F-actin quantity in a concentration-dependent way. However, the critical concentration of actin polymerization was unaltered. Thus, PEVK accelerates actin polymerization by facilitating its nucleation. This effect was highlighted in the AFM images of F-actin–PEVKII adsorbed to the supported lipid bilayer. The sample was dominated by radially symmetric complexes of short actin filaments. PEVK’s actin polymerization-modulating effect may, in principle, have a function in regulating sarcomeric actin length and turnover. Altogether, titin’s PEVK domain is not only a non-canonical actin-binding protein that regulates sarcomeric shortening, but one that may modulate actin polymerization as well.

Photosensitization has a wide range of applications in vastly distant fields. Three key components must be present at the same time to trigger the related photodynamic effect: light, the photosensitizer (PS) and oxygen. Irradiating the sensitizer leads to the formation of reactive oxygen species (ROS). Since PSs are accumulated preferably in lipid membranes, the study of photoinduced damage to membrane lipids can greatly increase our understanding of the effect of ROS on membranes in pathological as well as therapeutic conditions. We aimed to characterize the topographical and nanomechanical changes in supported lipid bilayers (SLBs) evoked by light-induced ROS formation. SLBs were prepared on mica surfaces by deposition of liposomes containing unsaturated lipid components. Topographical changes of SLBs were imaged by atomic force microscopy (AFM), and ROS-induced nanomechanical alterations of the membranes were assessed by AFM force measurements. To shed light on chemical alterations of the membrane constituents, infrared spectra were recorded. In the AFM images of porphyrin-containing membranes nanoscopic, bilayer-spanning holes were detected after irradiation. The measured rupture forces increased as a result of irradiation. These phenomena did not occur in membranes lacking unsaturated lipid components, emphasizing their role in ROS-mediated disruption confirmed by infrared spectroscopy results.

Hypercholesterolemia (HC) induces, propagates and exacerbates cardiovascular diseases via various mechanisms that are yet not properly understood. Extracellular vesicles (EVs) are involved in the pathomechanism of these diseases. To understand how circulating or cardiac-derived EVs could affect myocardial functions, we analyzed the metabolomic profile of circulating EVs, and we performed an in-depth analysis of cardiomyocyte (CM)-derived EVs in HC. Circulating EVs were isolated with Vezics technology from male Wistar rats fed with high-cholesterol or control chow. AC16 human CMs were treated with Remembrane HC supplement and EVs were isolated from cell culture supernatant. The biophysical properties and the protein composition of CM EVs were analyzed. THP1-ASC-GFP cells were treated with CM EVs, and monocyte activation was measured. HC diet reduced the amount of certain phosphatidylcholines in circulating EVs, independently of their plasma level. HC treatment significantly increased EV secretion of CMs and greatly modified CM EV proteome, enriching several proteins involved in tissue remodeling. Regardless of the treatment, CM EVs did not induce the activation of THP1 monocytes. In conclusion, HC strongly affects the metabolome of circulating EVs and dysregulates CM EVs, which might contribute to HC-induced cardiac derangements.

Background Evidence supporting the benefits of delayed cord clamping is increasing; however, there is no clear recommendation on cord management during newborn resuscitation. This study aimed to investigate the effects of resuscitation initiated with an intact umbilical cord, hypothesizing it is a safe stabilization procedure that improves neonatal outcomes. Methods Systematic search was conducted in MEDLINE, Embase, CENTRAL, and Web of Science from inception to March 1, 2024. Eligible articles compared neonatal outcomes in newborns receiving initial stabilization steps before and after cord clamping. Results Twelve studies met our inclusion criteria, with six RCTs included in the quantitative analysis. No statistically significant differences were found in delivery room parameters, in-hospital mortality, or neonatal outcomes between the examined groups. However, intact cord resuscitation group showed higher SpO 2 at 5 min after birth compared to cord clamping prior to resuscitation group (MD 6.67%, 95% CI [−1.16%, 14.50%]). There were no significant differences in early complications of prematurity (NEC ≥ stage 2: RR 2.05, 95% CI [0.34, 12.30], IVH: RR 1.25, 95% CI [0.77, 2.00]). Conclusion Intact cord management during resuscitation appears to be a safe intervention; its effect on early complications of prematurity remains unclear. Further high-quality RCTs with larger patient numbers are urgently needed. Impact Initiating resuscitation with an intact umbilical cord appears to be a safe intervention for newborns. No statistically significant differences were found in delivery room parameters, in-hospital mortality, and neonatal outcomes between the examined groups. The utilization of specialized resuscitation trolleys appears to be promising to reduce the risk of intraventricular hemorrhage in preterm infants. Further high-quality RCTs with larger sample sizes are urgently needed to refine recommendations.

Background The relationship between biomarkers of bone remodeling due to systematic training is not known, it is not possible to predict the optimal type and volume of exercise for bone remodeling. Objective We aimed to quantify the effects of systematic training on bone remodeling biomarkers, particularly osteocalcin and bone alkaline phosphatase in healthy adult populations. Methods This study (PROSPERO: CRD42023483811) explored the effects of systematic training (training programs lasting more than two weeks) through a systematic review and meta-analysis and included only randomized controlled trials of different types (endurance, power, and mixed) and intensities, frequency and duration of training. MEDLINE, Embase, and CENTRAL were searched on November 22, 2023, and we updated the search on 19, September 2025. Risk-of-bias and quality assessment were performed using the Cochrane Risk-of-Bias 2 (RoB2) tool and the GRADEpro Guideline Development Tool (GRADEpro). Results A total of 16,434 records were screened, and 24 studies with 1,238 participants were analyzed. Endurance training showed no significant effect on osteocalcin level. High- and low-intensity endurance training also had no significant effect on osteocalcin. High-intensity training significantly increased osteocalcin levels (MD = 6.88; 95% CI 0.37 to 13.38). Endurance training significantly decreased the Body Mass Index (MD = −1.40; 95% CI −2.23 to –0.57). Power training showed no significant change in osteocalcin levels. Mixed training (endurance + power) did not significantly change osteocalcin levels. Bone alkaline phosphatase showed no significant change following endurance training. Bone Mineral Density showed no significant changes after endurance or power training. The risk of bias was low for all outcomes. GRADEpro assessment for osteocalcin in the high-intensity training group revealed moderate to low certainty. Conclusion This is the first systematic review and meta-analysis on the effects of systematic training on bone biomarkers in healthy adults. Our findings show that high-intensity systematic training significantly decreases Body Mass Index and significantly increases osteocalcin levels, whereas other training types had no effect. Key Points This meta-analysis demonstrated a significant change in the bone remodeling marker osteocalcin only in response to systematic high-intensity training.   Intensity, rather than the type of exercise, plays a critical role in influencing bone remodeling. Systematic high-intensity training significantly reduces BMI, whereas power, mixed, low or moderate-to-high intensity endurance training shows no significant effect on bone mineral density.

Pancreatic cancer (PC) is one of the most lethal cancers worldwide. Recently, fatty pancreas (FP) has been studied thoroughly, and although its relationship to PC is not fully understood, FP is suspected to contribute to the development of PC. We aimed to assess the association between PC and FP by conducting a systematic review and meta-analysis. We systematically searched three databases, MEDLINE, Embase, and CENTRAL, on 21 October 2022. Case–control and cross-sectional studies reporting on patients where the intra-pancreatic fat deposition was determined by modern radiology or histology were included. As main outcome parameters, FP in patients with and without PC and PC in patients with and without FP were measured. Proportion and odds ratio (OR) with a 95% confidence interval (CI) were used for effect size measure. PC among patients with FP was 32% (OR 1.32; 95% CI 0.42–4.16). However, the probability of having FP among patients with PC was more than six times higher (OR 6.13; 95% CI 2.61–14.42) than in patients without PC, whereas the proportion of FP among patients with PC was 0.62 (95% CI 0.42–0.79). Patients identified with FP are at risk of developing PC. Proper screening and follow-up of patients with FP may be recommended.

The photodynamic effect requires the simultaneous presence of light, photosensitizer (PS) and molecular oxygen. In this process, the photoinduced damage of cells is caused by reactive oxygen species (ROS). Besides DNA, the other target of ROS is the membranes, separating internal compartments in living cells. Hence, the ability of ROS formation of porphyrins as PSs, in liposomes as simple models of cellular membranes is of outstanding interest. Earlier we compared the binding parameters and locations of mesoporphyrin IX dihydrochloride (MPCl) and mesoporphyrin IX dimethyl ester (MPE), in small unilamellar vesicles (SUV) made from various saturated phosphatidylcholines. In this study, we used the same kinds of samples for comparing the ROS forming ability. Triiodide production from potassium iodide because of light-induced ROS in the presence of molybdate catalyst was applied, and the amount of product was quantitatively followed by optical spectrometry. Furthermore, we demonstrated and carefully studied SUVs disruption as direct evidence of membrane destruction by the methods of dynamic light scattering (DLS) and fluorescence correlation spectroscopy (FCS), applying unsaturated phosphatidylcholines as membrane components. Although the ROS forming ability is more pronounced in the case of MPCl, we found that the measured disruption was more effective in the samples containing MPE.

Tuberculosis is one of the top ten causes of death worldwide, and due to the appearance of drug-resistant strains, the development of new antituberculotic agents is a pressing challenge. Employing an in silico docking method, two coumaran (2,3-dihydrobenzofuran) derivatives—TB501 and TB515—were determined, with promising in vitro antimycobacterial activity. To enhance their effectiveness and reduce their cytotoxicity, we used liposomal drug carrier systems. Two types of small unilamellar vesicles (SUV) were prepared: multicomponent pH-sensitive stealth liposome (SUVmixed) and monocomponent conventional liposome. The long-term stability of our vesicles was obtained by the examination of particle size distribution with dynamic light scattering. Encapsulation efficiency (EE) of the two drugs was determined from absorption spectra before and after size exclusion chromatography. Cellular uptake and cytotoxicity were determined on human MonoMac-6 cells by flow cytometry. The antitubercular effect was characterized by the enumeration of colony-forming units on Mycobacterium tuberculosis H37Rv infected MonoMac-6 cultures. We found that SUVmixed + TB515 has the best long-term stability. TB515 has much higher EE in both types of SUVs. Cellular uptake for native TB501 is extremely low, but if it is encapsulated in SUVmixed it appreciably increases; in the case of TB515, quasi total uptake is accessible. It is concluded that SUVmixed + TB501 seems to be the most efficacious antitubercular formulation given the presented experiments; to find the most promising antituberculotic formulation for therapy further in vivo investigations are needed.