Effectiveness and safety of Tachosil® as a ventricular sealant: an observational cohort study.

PURPOSE: Surgery close to or in contact with the ventricular system is challenging due to the complications. We sought to evaluate the effectiveness and safety of TachoSil® as a ventricular sealant in preventing complications after cranial surgery with an open ventricular system (OVS). METHODS: This is a single-center and prospective cohort study We included patients who underwent elective surgery for supratentorial craniotomy and periventricular pathology between December 2020 and November 2023. We registered surgical complications arising from CSF dynamics (such as percutaneous cerebrospinal fluid (CSF) leakage, hydrocephalus, pseudomeningocele), infections, and other complications (postsurgical hematoma) adverse drug reactions (ADRs), reintervention or hospital readmission up to 90 days after surgery. RESULTS: Forty interventions were performed on 39 patients, whose median age was 56 years. Eleven patients (28.2%) had antecedents of previous surgery in the same location, 5 (12.8%) had previously received radiotherapy and chemotherapy, and 11 (28.2%) were smokers. Twenty-four patients (60%) underwent surgery for high-grade glioma, 8 (20%) for low-grade gliomas, 6 (15%) for metastasis and 2 (5%) for meningioma. Throughout the study and up to 90 days after surgery, none of the patients presented an ADR. Only 2 patients (5%) presented with a surgery complications derived from ventricular opening (one patient with a percutaneous CSF leakage and one patients with external hydrocephalus). Both patients resolved with a ventriculoperitoneal shunt. CONCLUSIONS: TachoSil® is a dural sealant that can be used safely and effectively intraparenchymally in patients whose surgery involves a ventricular opening. Only 5% of treated patients presented complications arising from CSF hydrodynamics. No patients had pseudomeningocele, infections or complications related to the use of this sealant. To confirm these positive results, randomized and comparative clinical trials assessing the efficacy of TachoSil® in patients after cranial surgery with an OVS are essential. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: This study was registered in the Clinical Trials.gov (NCT05717335). Date May 1st, 2022.

Iron chelation as a new therapeutic approach to prevent senescence and liver fibrosis progression.

Iron overload and cellular senescence have been implicated in liver fibrosis, but their possible mechanistic connection has not been explored. To address this, we have delved into the role of iron and senescence in an experimental model of chronic liver injury, analyzing whether an iron chelator would prevent liver fibrosis by decreasing hepatocyte senescence. The model of carbon tetrachloride (CCl4) in mice was used as an experimental model of liver fibrosis. Results demonstrated that during the progression of liver fibrosis, accumulation of iron occurs, concomitant with the appearance of fibrotic areas and cells undergoing senescence. Isolated parenchymal hepatocytes from CCl4-treated mice present a gene transcriptomic signature compatible with iron accumulation and senescence, which correlates with induction of Reactive Oxygen Species (ROS)-related genes, activation of the Transforming Growth Factor-beta (TGF-ß) pathway and inhibition of oxidative metabolism. Analysis of the iron-related gene signature in a published single-cell RNA-seq dataset from CCl4-treated livers showed iron accumulation correlating with senescence in other non-parenchymal liver cells. Treatment with deferiprone, an iron chelator, attenuated iron accumulation, fibrosis and senescence, concomitant with relevant changes in the senescent-associated secretome (SASP), which switched toward a more anti-inflammatory profile of cytokines. In vitro experiments in human hepatocyte HH4 cells demonstrated that iron accumulates in response to a senescence-inducing reagent, doxorubicin, being deferiprone able to prevent senescence and SASP, attenuating growth arrest and cell death. However, deferiprone did not significantly affect senescence induced by two different agents (doxorubicin and deoxycholic acid) or activation markers in human hepatic stellate LX-2 cells. Transcriptomic data from patients with different etiologies demonstrated the relevance of iron accumulation in the progression of liver chronic damage and fibrosis, correlating with a SASP-related gene signature and pivotal hallmarks of fibrotic changes. Altogether, our study establishes iron accumulation as a clinically exploitable driver to attenuate pathological senescence in hepatocytes.

Update on ketosis in dairy cattle with major emphasis on subclinical ketosis and abdominal adiposity.

The metabolic changes that occur during the early post-partum period in dairy cows can indeed lead to an imbalance in energy utilization, resulting in the production of excessive ketone bodies. This can have detrimental effects on the cow's health and milk production, leading to economic losses for dairy producers. The release of non-esterified fatty acids into the blood due to increased lipolysis is a key factor in the development of ketosis. Abdominal adiposity is a key factor on these outcomes in modern dairy cows. The redirection of energy and glucose towards lactose synthesis and milk yield leaves a deficit of gluconeogenic precursors, leading to the conversion of acetyl-CoA into ketone bodies instead of entering the Krebs cycle. These ketone bodies, including acetone, acetoacetate and ß-hydroxybutyrate, accumulate in the blood and can be detected in various bodily fluids, such as urine, blood and milk, allowing for diagnostic testing. Prevention is indeed crucial in managing ketosis in dairy cattle. Supplementation of propylene glycol in the diet or the use of monensin, either in the diet or in the form of a slow-release bolus, can help prevent the occurrence of ketosis. However, avoiding high body condition (subcutaneous fat) and excessive abdominal adiposity during the dry period and parturition plus an adequate cow comfort are fundamental tasks to avoid ketosis and related disorders. These interventions aim to provide additional energy sources or enhance the cow's ability to utilize energy efficiently, thus reducing the reliance on excessive lipolysis and ketone body production.

Release of mitochondrial dsRNA into the cytosol is a key driver of the inflammatory phenotype of senescent cells.

The escape of mitochondrial double-stranded dsRNA (mt-dsRNA) into the cytosol has been recently linked to a number of inflammatory diseases. Here, we report that the release of mt-dsRNA into the cytosol is a general feature of senescent cells and a critical driver of their inflammatory secretome, known as senescence-associated secretory phenotype (SASP). Inhibition of the mitochondrial RNA polymerase, the dsRNA sensors RIGI and MDA5, or the master inflammatory signaling protein MAVS, all result in reduced expression of the SASP, while broadly preserving other hallmarks of senescence. Moreover, senescent cells are hypersensitized to mt-dsRNA-driven inflammation due to their reduced levels of PNPT1 and ADAR1, two proteins critical for mitigating the accumulation of mt-dsRNA and the inflammatory potency of dsRNA, respectively. We find that mitofusin MFN1, but not MFN2, is important for the activation of the mt-dsRNA/MAVS/SASP axis and, accordingly, genetic or pharmacologic MFN1 inhibition attenuates the SASP. Finally, we report that senescent cells within fibrotic and aged tissues present dsRNA foci, and inhibition of mitochondrial RNA polymerase reduces systemic inflammation associated to senescence. In conclusion, we uncover the mt-dsRNA/MAVS/MFN1 axis as a key driver of the SASP and we identify novel therapeutic strategies for senescence-associated diseases.

Immune dysregulation is an important factor in the underlying complications in Influenza infection. ApoH, IL-8 and IL-15 as markers of prognosis.

Introduction: Influenza virus infection can cause a range of clinical symptoms, including respiratory failure (RF) and even death. The mechanisms responsible for the most severe forms of the disease are not yet well understood. The objective is to assess the initial immune response upon admission and its potential impact on infection progression. Methods: We conducted a prospective observational study of patients with influenza virus infection who required admission to a tertiary hospital in the 2017/18 and 2018/19 flu seasons. Immune markers, surrogate markers of neutrophil activation, and blood levels of DNase I and Apolipoprotein-H (ApoH) were determined in the first serum sample available during hospital care. Patients were followed until hospital discharge or death. Initially, 792 patients were included. From this group, 107 patients with poor evolution were selected, and a random control group was matched by day of admission. Results: Patients with poor outcomes had significantly reduced ApoH levels, a soluble protein that regulate both complement and coagulation pathways. In multivariate analysis, low plasma levels of ApoH (OR:5.43; 2.21-13.4), high levels of C- reactive protein (OR:2.73: 1.28-5.4), hyperferritinemia (OR:2.83; 1.28-5.4) and smoking (OR:3.41; 1.04-11.16), were significantly associated with a worse prognosis. RF was independently associated with low levels of ApoH (OR: 5.12; 2.02-1.94), while high levels of IL15 behaved as a protective factor (OR:0.30; 0.12-0.71). Discussion: Therefore, in hospitalized influenza patients, a dysregulated early immune response is associated with a worse outcome. Adequate plasma levels of ApoH are protective against severe influenza and RF and High levels of IL15 protect against RF.

A pattern emerges in chromatin aging: AP-1 steals the show.

During aging, transcriptional programs of cell identity are partially eroded, reducing cellular fitness and resilience. Patrick et al.1 unveil a general mechanism for this process that consists of the progressive loss of transcription factor AP-1 from cell identity enhancers and its relocation by competition to stress-response elements.

Carotid Intima-Media Thickness, Overweight, and Poor Sleep Quality in Commercial Airline Pilots: A Cross-Sectional Study.

Background Cardiovascular disease is a leading cause of premature career termination in commercial airline pilots (APs). In this cross-sectional study, we sought to investigate the relationship between intima-media thickness (IMT), a marker of subclinical atherosclerosis, and cardiovascular risk factors in APs, focusing on overweight status and sleep quality. Methods A total of 140 male APs were categorized into four groups based on body mass index (BMI) and Pittsburgh Sleep Quality Index (PSQI) score: overweight poor sleepers (OW-PS), overweight good sleepers (OW-GS), normal weight poor sleepers (NW-PS), and normal weight good sleepers (NW-GS). IMT was quantified in the common carotid artery (CCA) and carotid bulb using ultrasound, yielding a composite IMT (IMTcom) measure. Common cardiovascular risk factors were assessed in all participants. Results The prevalence of overweight and poor sleep quality was 43.6% and 32.9%, respectively. The OW-PS group had significantly higher age, heart rate, total cholesterol, and low-density lipoprotein (LDL) cholesterol compared to other groups (p<0.05). Overweight pilots, regardless of sleep quality, had increased IMTcom compared to normal-weight pilots (p<0.001). Age and LDL cholesterol were independent predictors of IMTcom in the OW-PS and OW-GS groups (p<0.05). Conclusions Overweight status, irrespective of sleep quality, is associated with increased IMT in APs, suggesting a higher burden of subclinical atherosclerosis. Interventions focused on reducing LDL cholesterol levels and managing age-related cardiovascular risk factors could be advantageous in mitigating the risk of atherosclerotic vascular disease in overweight pilots.

Corrigendum: Immune dysregulation is an important factor in the underlying complications in Influenza infection. ApoH, IL-8 and IL-15 as markers of prognosis.

[This corrects the article DOI: 10.3389/fimmu.2024.1443096.].

ImAge quantitates aging and rejuvenation.

For efficient, cost-effective and personalized healthcare, biomarkers that capture aspects of functional, biological aging, thus predicting disease risk and lifespan more accurately and reliably than chronological age, are essential. We developed an imaging-based chromatin and epigenetic age (ImAge) that captures intrinsic age-related trajectories of the spatial organization of chromatin and epigenetic marks in single nuclei, in mice. We show that such trajectories readily emerge as principal changes in each individual dataset without regression on chronological age, and that ImAge can be computed using several epigenetic marks and DNA labeling. We find that interventions known to affect biological aging induce corresponding effects on ImAge, including increased ImAge upon chemotherapy treatment and decreased ImAge upon caloric restriction and partial reprogramming by transient OSKM expression in liver and skeletal muscle. Further, ImAge readouts from chronologically identical mice inversely correlated with their locomotor activity, suggesting that ImAge may capture elements of biological and functional age. In sum, we developed ImAge, an imaging-based biomarker of aging with single-cell resolution rooted in the analysis of spatial organization of epigenetic marks.

Exploring the Interplay between Cellular Senescence, Immunity, and Fibrosing Interstitial Lung Diseases: Challenges and Opportunities.

Fibrosing interstitial lung diseases (ILDs) are characterized by the gradual and irreversible accumulation of scar tissue in the lung parenchyma. The role of the immune response in the pathogenesis of pulmonary fibrosis remains unclear. In recent years, substantial advancements have been made in our comprehension of the pathobiology driving fibrosing ILDs, particularly concerning various age-related cellular disturbances and immune mechanisms believed to contribute to an inadequate response to stress and increased susceptibility to lung fibrosis. Emerging studies emphasize cellular senescence as a key mechanism implicated in the pathobiology of age-related diseases, including pulmonary fibrosis. Cellular senescence, marked by antagonistic pleiotropy, and the complex interplay with immunity, are pivotal in comprehending many aspects of lung fibrosis. Here, we review progress in novel concepts in cellular senescence, its association with the dysregulation of the immune response, and the evidence underlining its detrimental role in fibrosing ILDs.

Brushing Away the Blues: Self-Reported Oral Hygiene Practices Are Associated With Mild Depressive Symptoms in Airline Pilots.

Introduction Airline pilots are susceptible to mental health issues, with depression prevalence ranging from 1.9% to 12.6%. Recent research in the general population indicates a potential link between depression and oral health. In this cross-sectional study, we sought to investigate the association between self-reported oral hygiene practices and depressive symptoms among airline pilots. Methods One hundred actively working male airline pilots of Caucasian descent voluntarily enrolled in the study during routine occupational health visits. Depressive symptoms were assessed using the Beck Depression Inventory II (BDI-II). Self-reported oral hygiene practices, including toothbrushing frequency and mouthwash usage, were examined. Univariable and multivariable logistic regression analyses were performed to investigate associations between depressive symptoms and oral hygiene practices. Results Twelve pilots (12%) demonstrated mild depressive symptomatology (BDI-II scores 14-19). Pilots with mild depression reported significantly lower rates of brushing teeth twice or more per day (33.3% vs. 80.7%) and higher rates of rarely brushing (16.7% vs. 1.1%) compared to those with minimal depressive symptoms (p < 0.001). Nonuse of mouthwash was more prevalent among pilots with mild depression (66.6% vs. 23.9%, p = 0.008). Multivariable logistic regression analysis revealed that pilots who rarely brushed their teeth (adjusted odds ratio (OR) = 14.6; 95% confidence interval (CI) = 1.3-197.9; p < 0.05) or did not use mouthwash (adjusted OR = 5.7; 95% CI = 1.4-25.2; p < 0.05) had significantly higher odds of mild depressive symptoms. Conclusions Self-reported oral hygiene habits may serve as a proxy indicator for mild depressive symptoms among airline pilots. Incorporating oral health assessments into routine aeromedical examinations could provide a practical method of identifying pilots at risk for depression, supporting timely interventions and enhancing flight safety.

Developmental origin of oligodendrocytes determines their function in the adult brain.

In the mouse embryonic forebrain, developmentally distinct oligodendrocyte progenitor cell populations and their progeny, oligodendrocytes, emerge from three distinct regions in a spatiotemporal gradient from ventral to dorsal. However, the functional importance of this oligodendrocyte developmental heterogeneity is unknown. Using a genetic strategy to ablate dorsally derived oligodendrocyte lineage cells (OLCs), we show here that the areas in which dorsally derived OLCs normally reside in the adult central nervous system become populated and myelinated by OLCs of ventral origin. These ectopic oligodendrocytes (eOLs) have a distinctive gene expression profile as well as subtle myelination abnormalities. The failure of eOLs to fully assume the role of the original dorsally derived cells results in locomotor and cognitive deficits in the adult animal. This study reveals the importance of developmental heterogeneity within the oligodendrocyte lineage and its importance for homeostatic brain function.

Efficacy and Safety of Two Chondroprotective Supplements in Patients With Knee Osteoarthritis: A Randomized, Single-Blind, Pilot Study.

Background: Hyaluronic acid (HA), glucosamine (Glc), and chondroitin sulfate (CS) are key ingredients commonly incorporated into dietary chondroprotective supplements for the management of osteoarthritis (OA). Despite their widespread use, there is a paucity of published data regarding their efficacy and safety, necessitating rigorous investigation in clinical settings. To address this knowledge gap, we conducted a randomized, single-blind pilot study to evaluate the effects of two commercially available multi-ingredient supplements on patients with mild-to-moderate knee OA. Methods: A total of 51 patients diagnosed with mild-to-moderate knee OA were enrolled in a four-week randomized study and allocated equally (1:1:1 ratio) into three groups: a control group (n = 17) that received no treatment, an HA group (n = 17) given Syalox® 300 Plus (1 tablet/day) containing HA (300 mg) and Boswellia serrata extract (100 mg), and a Glc + CS group (n = 17) given Cartijoint® Forte (1 tablet/day) containing Glc (415 mg), CS (400 mg), and curcuminoids from rhizomes of Curcuma longa L (50 mg).Physicians conducting evaluations were blinded to group assignments, whereas patients were not. All participants underwent assessments of pain relief, functional capacity improvement, and serum adropin levels, an emerging biomarker of knee OA, at baseline and after the four-week intervention period. Results: Both the HA and the Glc + CS groups exhibited improvements at the end of the study relative to baseline, with statistically significant differences (p < 0.05) observed in pain at rest, pain during movement, range of motion, and the overall Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores, including its pain, stiffness, and physical function subscales. Notably, the HA group outperformed the Glc + CS group in the alleviation of pain at rest, pain during movement, and on the WOMAC pain subscale, with all differences being statistically significant (p < 0.05). Additionally, both groups showed a significant elevation in serum adropin levels from baseline (p < 0.05), with the HA group experiencing a more substantial increase when compared to the Glc + CS group (p < 0.05). Both supplements showed a limited number of treatment-emergent adverse events. Conclusion: Oral supplementation with either HA or Glc + CS demonstrated potential benefits for managing symptoms of mild-to-moderate knee OA. Notably, HA supplementation was associated with greater improvements in pain relief and higher elevations in serum adropin levels compared to Glc + CS supplementation. However, larger-scale and longer-term studies are necessary to further evaluate the safety and efficacy of these dietary supplements within the clinical management arsenal for knee OA.

Occupational Health Challenges for Aviation Workers Amid the Changing Climate: A Narrative Review.

Although there are many forecasts regarding the impact of climate change on the aviation sector, a critical but frequently neglected dimension is the occupational safety risks faced by aviation professionals. This narrative review explores the potential impacts of the changing climate on the health and safety of aviation personnel. Furthermore, we examine the significance of resilience in helping these workers adapt and effectively manage climate-related challenges in their professional lives. Climate change poses increasing threats to the well-being of flight personnel through elevated temperatures, heightened ultraviolet radiation exposure, increased mental workload from extreme weather events, and other psychological stressors. Building resilience through workforce training, planning, and adaptation can reduce vulnerability. In future research, the iterative process of selecting measurement components to gauge the impact of climate change should balance feasibility, relevance for stakeholders, and accurately capturing exposure effects. For instance, while salivary cortisol measures stress biologically, assessments of depression or burnout may provide more nuanced insights on pilot health for industry decision-makers managing climate impacts. In conclusion, a strategic emphasis on enhancing the physical and psychological well-being of the aviation workforce is imperative for facilitating a more efficient adaptation within the sector. This is of paramount importance, considering the critical function that aviation serves in fostering human connectivity. Consequently, it is essential for regulatory bodies and policymakers to prioritize the safeguarding of employee health in the face of climate change challenges.

Serum Prestin and Otolin-1 Levels in Pilots of Helicopter-Based Emergency Medical Services: Potential Markers for Ear Injury.

INTRODUCTION: Occupational noise exposure is a major public health concern, impacting a large workforce worldwide. In this study, we sought to evaluate the serum concentrations of prestin, a cochlear protein that diminishes following noise exposure, and otolin-1, a protein secreted into the bloodstream subsequent to inner ear damage, among three diverse professional categories, each exposed to varying degrees of noise. Helicopter emergency medical service (HEMS) pilots and construction workers were considered high-risk groups due to their elevated exposure to occupational noise, whereas office workers were regarded as a low-risk group, reflecting their comparatively minimal noise exposure. METHODS: The study sample included 60 males, encompassing helicopter pilots, construction laborers, and office workers (n=20, each). Recruitment occurred during standard occupational health visits, with all participants presenting normal clinical audiograms. Serum levels of prestin and otolin-1 were measured in duplicate using commercially available immunoassays and compared across the three professional categories. RESULTS: HEMS pilots had the lowest mean serum prestin level at 211±27 pg/mL, followed by construction workers at 234±29 pg/mL, and office workers at 269±42 pg/mL (p<0.001, one-way analysis of variance), with all inter-group differences statistically significant (p<0.05, Tukey's post hoc tests). For otolin-1, HEMS pilots showed the highest mean at 216±20 pg/mL, with construction workers at 196±22 pg/mL, and office workers at 181±20 pg/mL (p<0.001, one-way analysis of variance). Statistically significant differences were found between HEMS pilots and both other groups for otolin-1 levels (p<0.05, Tukey's post hoc tests), but not between construction workers and office workers. CONCLUSIONS:  Serum concentrations of prestin and otolin-1 may differ among healthy individuals according to their occupational noise exposure and have the potential to act as indicators of subclinical inner ear injury. To substantiate these preliminary observations, incorporating exposure assessment, especially via direct measurements of noise and vibration exposure, would markedly improve the reliability of our findings.

Successful Management of Chronic Wounds by an Autophagy-Activating Magnetized Water-Based Gel in Elderly Patients: A Case Series.

Chronic wounds pose a significant threat to human health, particularly for the elderly, and require extensive healthcare resources globally. Autophagy, a key molecular player in wound healing, not only offers a defense against infections but also contributes to the deposition of the extracellular matrix during the proliferative phase. Additionally, it promotes the proliferation and differentiation of endothelial cells, fibroblasts, and keratinocytes. We have recently shown that applying magnetized saline water topically can trigger autophagy in intact skin. In this case series, we document the successful management of five non-infected, difficult-to-heal wounds in elderly patients using a topical autophagy-stimulating gel containing 95% magnetized saline water. The treated wounds included pressure ulcers, venous ulcers, and trauma-related injuries that had shown minimal or no improvement with standard wound therapies over a prolonged period. Application of the autophagy-stimulating gel promoted wound healing, as indicated by reduced fibrous and necrotic tissue, granulation tissue formation, re-epithelialization, and partial or complete wound closure. These preliminary case studies suggest that a topical gel containing magnetized saline water, which promotes autophagy, may aid healing of chronic wounds in elderly patients. Further investigation is warranted to explore the potential of this novel approach, as it may offer a valuable addition to the existing arsenal of wound care treatments for the aging population, particularly in addressing difficult-to-heal wounds.

Correction: Limited Role of Murine ATM in Oncogene-Induced Senescence and p53-Dependent Tumor Suppression.

[This corrects the article DOI: 10.1371/journal.pone.0005475.].

Relation of Sleep Quality to a Panel of Plasma Cardiometabolic Markers in Airline Pilots: A Cross-Sectional Study.

Background Insomnia and poor sleep are leading modifiable risk factors for cardiovascular disease. Given the high susceptibility of airline pilots (APs) to sleep disturbances, we sought to investigate the hypothesis that poor sleep in this professional group correlates with alterations in plasma biochemical markers that would reflect critical aspects in the pathophysiology of cardiometabolic disorders. Methods In this preliminary cross-sectional study, we examined the relation of poor sleep to fourteen plasma biomarkers reflecting multiple cardiometabolic pathways in a convenience sample of 117 male APs. The Pittsburgh Sleep Quality Index (PSQI) was used to categorize the participants into good sleepers (n = 70, 59.8%; PSQI scores from 0 to 4) and poor sleepers (n = 47, 40.2%; PSQI scores of 5 or higher). The concentrations of biomarkers were compared between the two groups using both univariable and multivariable analyses. Results Compared to good sleepers, APs identified as poor sleepers exhibited significantly different levels of four plasma cardiometabolic biochemical markers in univariable analysis. However, in multivariable-adjusted analysis, only three biomarkers, adiponectin, fibroblast growth factor (FGF)-21, and growth differentiation factor (GDF)-15, remained independently associated with poor sleep. Conclusion Poor sleep quality in APs correlates with lower plasma concentrations of adiponectin and elevated levels of FGF-21 and GDF-15. Further longitudinal studies are required to elucidate the role of these biomarkers in the link between sleep disturbances and cardiometabolic risk in this professional group.

Probiotic Supplementation With Saccharomyces boulardii and Enterococcus faecium Improves Gastric Pain and Bloating in Airline Pilots With Chronic Non-atrophic Gastritis: An Open-Label Study.

Background Commercial airline pilots (APs) are prone to upper gastrointestinal symptoms, such as epigastric pain and bloating. These issues are often linked to occupational risk factors like irregular diet, sleep disruption, and circadian rhythm disturbance. The use of probiotics to enhance intestinal health is well established, but their efficacy in treating upper gastrointestinal diseases is still debated. This is primarily due to the stomach's small resident microbiota and its low pH, which is inhospitable to most microbes. However, emerging research suggests that specific probiotic strains, such as Enterococcus faecium, can withstand acidic environments. Moreover, certain yeast species, including Saccharomyces boulardii, can survive at a low pH. Consequently, we conducted a preliminary, three-arm, randomized, open-label, dose-finding, four-week study to compare the effects of watchful waiting (WW) with the administration of an oral probiotic supplement containing S. boulardii and E. faecium in APs diagnosed with Helicobacter pylori-negative chronic non-atrophic gastritis (CNG). Methods The study included 39 APs with CNG who were randomized into three groups with a 1:1:1 ratio. The low-dose group (n = 13) received one capsule of the probiotic supplement twice daily, before meals, for four weeks. The high-dose group (n = 13) was administered two capsules of the supplement on the same schedule. The third group (n = 13) underwent WW and served as the control arm. Blinding was maintained for the examining physicians and laboratory staff, but not for the patients. All participants self-rated their experiences of gastric pain and bloating at the beginning and conclusion of the four-week treatment period. Additionally, serum levels of pepsinogen I (PGI) and pepsinogen II (PGII) were measured at these time points. Results Supplementation with probiotics significantly outperformed WW in reducing subjective gastric pain and bloating. This effect was consistent across both tested dosages, with no significant differences observed. However, only high-dose probiotics led to a statistically significant decrease in PGII levels and an increase in the PGI/PGII ratio after the four-week study period, a result not observed with low-dose probiotics. Conclusions Oral administration of S. boulardii and E. faecium demonstrated potential efficacy in reducing gastric pain and bloating symptoms in APs with CNG, as evidenced by statistically significant symptom improvement compared to the control group that did not receive the probiotic supplementation. Notably, high-dose probiotics resulted in a significant increase in the PGI/PGII ratio, indicating potential long-term cytoprotective effects on the gastric mucosa.

Mucosal TLR5 activation controls healthspan and longevity.

Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.