Biomedicines最新文献

The journal retracts the article "High PGC-1α Expression as a Poor Prognostic Indicator in Intracranial Glioma" [...].

Background/Objectives: Chronic hepatitis C virus (HCV) infection remains a significant comorbidity in patients with end-stage renal disease (ESRD), complicating outcomes after kidney transplantation. The anti-viral treatment of HCV infection including Direct-acting antivirals (DAAs) have transformed HCV treatment, but evidence remains limited. Methods: We conducted a retrospective, real-world cohort study using the TriNetX Analytics Network. Patients were divided into two cohorts: those who received anti-viral treatment of HCV infections before transplant (n = 982) and those who did not (n = 982), following 1:1 propensity score matching. Results: Outcomes assessed one year post-index included mortality, hepatic complications, graft failure, and serum creatinine >6 mg/dL. Anti-HCV infection treated patients had significantly lower risks of graft failure (aHR: 0.656; 95% CI: 0.434, 0.993; p < 0.001) and severe renal dysfunction (aHR: 0.619; 95% CI: 0. 0.390, 0.984; p < 0.001) compared to untreated patients. While mortality (aHR: 0.901; 95% CI: 0.728, 1.114) and liver-related outcomes trended favorably in the treated group, they did not reach statistical significance. Conclusions: Our findings demonstrate that pre-transplant anti-viral treatment of HCV infection in HCV-infected kidney transplant recipients is associated with improved graft survival and renal function.

Myocardial infarction (MI) and depression exhibit a bidirectional relationship, in which patients with MI are more susceptible to depression, and individuals with depression face a heightened risk of MI. The two diseases are intricately intertwined via the heart-brain axis. Sex, age, lifestyle, social background, comorbidities, and genetics contribute to and affect the prognosis of this combined condition. Mechanisms involving the autonomic nervous system (ANS), hypothalamic-pituitary-adrenal (HPA) axis, inflammation, thrombosis, tryptophan metabolism, renin-angiotensin-aldosterone system (RAAS), endothelial dysfunction, microRNAs, and gut microbiota, as components of the heart-brain axis, have been implicated in the pathological link between MI and depression. This review outlines the common risk factors and potential mechanisms underlying this bidirectional relationship. It treats the comorbidities of MI and depression as a unified condition, relying on evidence from clinical trials and experimental studies that directly address both diseases together rather than extrapolating from separate studies on MI or depression alone. It also discusses current therapeutic approaches, including non-pharmacological interventions like psychotherapy and exercise, and pharmacological treatments with chemical or natural compounds. Finally, this review identifies significant gaps in the pathophysiology and clinical management of MI with depression, which warrant further investigation.

Periodontitis is a prevalent chronic inflammatory disease that leads to the progressive destruction of periodontal tissues and remains the primary cause of tooth loss worldwide. Despite advances in regenerative approaches-including stem cell therapy, scaffold-based tissue engineering, and guided tissue regeneration-the complete and functional restoration of the periodontal ligament remains a major clinical challenge. Stem-cell-based therapies and advanced biomaterials have emerged as promising strategies in regenerative medicine, offering potential for restoring periodontal structure and function. Among cells, periodontal-ligament-derived stem cells (PDLSCs) show exceptional regenerative potential due to their ability to differentiate into cementoblasts, osteoblasts, and other cell types essential for periodontal repair. In recent years, a variety of biomaterials with distinct specifications and properties have been utilized to repair periodontal damage. In addition to the inherent properties of biomaterials, the morphology and structural characteristics of these materials as bioequivalents for periodontal regeneration are also critical considerations. Furthermore, recent studies emphasize that mechanical stimulation plays a considerable role in directing stem cell differentiation, gene expression, matrix organization, and modulating inflammatory responses in periodontal regeneration. Canonical parameter ranges for systematic analysis indicate that cyclic stretch strain of 1-20% at 0.1-0.5 Hz (6-30 cycles/min) typically increases the expression of osteogenic markers (RUNX2, ALP, OCN) and matrix components (Col1) in PDLSCs. Conversely, higher values (>15%) often bias the response toward inflammatory pathways (IL-6, PGE2). Static compression above 2 g/cm² consistently stimulates the secretion of pro-inflammatory cytokines (IL-6, IL-8) and alters the RANKL/OPG balance in favor of osteoclastogenesis. Significant heterogeneity in response across studies will be analyzed by examining key methodological variables, including specific loading regimens (duration, frequency patterns) and culture conditions (e.g., serum/osteogenic supplements), which critically modulate mechanotransduction outcomes. This review summarizes current progress in periodontal regenerative medicine, emphasizing cellular and biomaterial considerations, as well as biofabrication techniques, with a particular focus on the influence of mechanical forces on PDLSCs. We discuss cellular responses to mechanical stimuli, including changes in gene expression, cytoskeletal organization, proliferation, and differentiation. Combining biological knowledge with advances in bioprinting and the study of mechanobiology, we finally discuss promising opportunities for improving periodontal regeneration that can be applied in the future in clinical practice.

Background/Objectives: Pediatric periodontal inflammation arises from complex host-microbe interactions. Beyond bacterial biofilms, fungal colonization-particularly by Candida albicans-is increasingly recognized as a contributor. The aim of this study was to investigate the relationship between fungal and bacterial colonization, host inflammatory mediators, and salivary parameters in children. It also aimed to identify salivary biomarkers that could be useful for the early diagnosis of oral candidiasis and periodontal inflammation. Methods: A cross-sectional study was performed on 140 children (8-15 years): healthy controls (n = 70) and cases with oral candidiasis (n = 70). Clinical indices (Plaque Index, Gingival Index, Bleeding on Probing), salivary flow, pH, and buffering capacity were recorded. Quantitative PCR assessed C. albicans and four periodontal pathogens, while ELISA measured salivary cytokines (IL-1β, IL-6, TNF-α, IL-8). Analyses included group comparisons, correlations, regression modeling, and principal component analysis (PCA). Results: Children with candidiasis exhibited higher PI, GI, and BOP (p < 0.001), along with reduced pH and buffering capacity (p < 0.001). Salivary loads of C. albicans and all targeted pathogens were elevated (p < 0.001). Cytokine levels were markedly increased (p < 0.001). GI correlated with C. albicans (ρ = 0.71) and cytokines (ρ = 0.62-0.76). Logistic regression identified C. albicans and IL-1β as independent predictors, while salivary pH and flow were found to be protective. PCA distinguished groups, with PC1 (55.2%) driven by fungal and cytokine markers. Conclusions: Oral candidiasis in children is defined by distinct microbial and inflammatory profiles. Salivary biomarker integration offers potential for early, non-invasive diagnosis and risk stratification.

Background: Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS) is a life-threatening complication of immune recovery, often triggered by antiretroviral therapy and characterized by Th1-skewed CD4⁺ T cell hyperactivation, neuroinflammation, and pulmonary dysfunction. Methods: Using a validated murine model of unmasking C-IRIS, we assessed the therapeutic potential of star-shaped glatiramer acetate (sGA), a structurally enhanced derivative of the FDA-approved immunomodulator glatiramer acetate (GA). sGA was administered intraperitoneally on days 1 and 3 post-CD4⁺ T cell reconstitution. Results: sGA significantly ameliorated C-IRIS-associated respiratory dysfunction, including increasing breaths per minute by ~35% and improved minute volume, total respiratory cycle time, expiration time, and inspiration time. Survival rate grew to 75% on day 14 for sGA-treated C-IRIS mice. In both the lung and the brain, sGA reduced total CD4⁺ T cells and selectively diminished Th1 cells by 50-60% and Th17 cells by 40-50%. Activated microglia decreased by 45% within the brain, indicating attenuated innate immune activation. Golgi-Cox analysis revealed region-specific neuroprotection: neuronal loss in the prefrontal cortex, lateral hypothalamus, and periaqueductal gray was rescued by 25-40%, whereas hippocampal neurons were relatively preserved, and basolateral amygdala neurons showed no significant recovery. Conclusion: Collectively, our findings suggest that sGA exerts neuroprotection in C-IRIS by limiting peripheral CD4⁺ T cell effector activity and suppressing CNS-resident immune activation. This study supports the use of sGA as a promising preclinical therapeutic candidate for C-IRIS and other Th1-mediated neuroinflammatory conditions.

Background: Many literature studies have reported the beneficial effects of probiotics on human health, but few articles have evaluated their "real effects" on the modulation of microbiota after their use. Lactobacillus reuteri (L. reuteri) is one of the most studied probiotics with the best effects on gut microbiota. Aims: The primary aim of our study was the evaluation of the intestinal colonization by L. reuteri-LMG P 27481 and its effects on the modification of the gut bacterial flora. The secondary aim was the evaluation of side effects through the validated Gastrointestinal Symptom Rating Scale (GSRS). Patients and Methods: This is an interventional, open-label study conducted on 20 healthy adults (10 men and 10 women M/F; mean age 34 ±15 years) who received a probiotic Reuterin^® LMG (L. reuteri LMG P 27481) for 28 consecutive days in drops at a concentration of 1 × 10⁹ (five drops per day). Microbiota analysis was performed at enrollment (T0), at the end of probiotic supplementation (T1) and after a 14-day follow-up period (T2). Results: In our study we observed interesting quantitative and functional variations as regards the Firmicutes/Bacterioidetes ratio, intestinal permeability, and the production of short-chain fatty acids (SCFA). This probiotic was safe and was able to improve patients' symptoms. Conclusions: The intake of L. reuteri LMG-P 27481 in healthy subjects showed transitory variations in some functional and metabolic gut functions, especially an improvement in the barrier effect and intestinal permeability, y and an increase in SCFA. Future studies should include target populations to have a greater range for modulation of the gut microbiota.

Background/Objective: The effectiveness of blue-light phototherapy (PT) is mainly dependent on the total dose of light (time under PT and amount of skin exposed) received by infants. The primary aim of this study was the development of a novel, flexible, and stretchable device to provide continuous PT treatment, avoiding temporary interruptions that are often observed in practice, such as during breastfeeding, for example. This study evaluated the biocompatibility of a novel, low-cost blanket equipped with light-emitting diode (LED) lamps designed to maintain therapeutic efficacy while facilitating uninterrupted skin-to-skin contact. Methods: Fourteen New Zealand White rabbits, weighing approximately 2.9 kg and aged 4 months, were randomly assigned to an experimental group (TG, n = 7) or a control group (CG, n = 7). The TG received phototherapy directly on the skin (irradiance: 19.3 [13.0-22.0] µW/cm^-2/nm^-1) during two 12 h sessions over consecutive days, while the CG remained under identical conditions with the device turned off. Biochemical, hematological, dermatological, and histological parameters, as well as rectal and skin temperatures, were assessed. Results: The results showed no differences in clinical appearance or histological analysis of skin tissue between the groups. Blood analysis indicated a reduction in absolute monocyte counts in the TG compared to the CG (p = 0.049), though levels remained within normal ranges. Skin temperature was consistently higher in the TG, except during the initial measurement. Rectal temperatures were similar on the first day but lower in the TG on the second day (mean 40.3 ± 0.21 °C vs. 40.7 ± 0.32 °C; p = 0.039). Conclusions: Temperature levels remained within physiological limits for both groups throughout the study. The device demonstrated biocompatibility and caused no adverse dermatological, hematological, or biochemical effects.

Background/Objectives: All-trans retinoic acid (atRA), a potent derivative of vitamin A, is recognized as a significant teratogen for inducing cleft palate in both humans and mice. The molecular mechanisms underlying it remain intricate and incompletely elucidated. The advent of single-cell sequencing technology offers novel methodologies to investigate the mechanisms by which atRA induces cleft palate. Methods: In this study, we use C57BL/6 mice to conduct cleft palate models, comprising a control group and an atRA-exposed group. Palatal shelves were collected at embryonic day 12.5 (E12.5) for 10x single-cell sequencing analysis to discern and compare the cellular and molecular disparities between the two groups. Validation of the findings was performed using Quantitative real-time polymerase chain reaction and Western blot techniques. Results: The findings indicate that at E12.5, atRA predominantly affects the mesenchymal and epithelial cells of the palatal shelves, inhibiting cellular proliferation and migration. The primary mechanism of atRA's effect involves modulation of the Wnt and TGF-β signaling pathways. Furthermore, the Ppp1r14b gene was identified as a critical mediator in atRA's interaction with these pathways. Conclusions: This study provides a more comprehensive understanding of the mechanisms underlying atRA-induced cleft palate formation. It highlights the significance of the Wnt and TGF-β pathways, as well as the Ppp1r14b gene during this procedure.

Background: Following myocardial infarction (MI), cardiac fibroblasts (CFs) adopt distinct phenotypes to ensure scar formation and healing. Although leukocytes are a critical driver of post-MI healing, the role of neutrophils in modulating CF phenotype remains insufficiently explored. We therefore investigated the impact of soluble mediators released by neutrophil subtypes found post-MI-pro-inflammatory (N1) and anti-inflammatory (N2)-on shaping CFs phenotype. Methods: In vitro, human 3D grown CFs were indirectly co-cultured with N1 or N2 neutrophil-like cells using a two-chamber Transwell system. After 24 h, expression of inflammatory, remodeling, and pro-fibrotic markers was evaluated in fibroblasts and conditioned media. In vivo, soluble mediators derived from polarized mouse neutrophils (SN1 or SN2) were injected into the infarcted myocardium of C57BL/6J after MI surgery. The effects on the healing process were investigated at 1 and 7 days post-MI. Results: In vitro, CFs were found to exhibit a pro-inflammatory and matrix-degrading phenotype following indirect co-culture with N1 cells, characterized by overexpression of IL-1β, IL-6, MCP-1, and metalloproteases MMP-3/MMP-9. In vivo, both SN1 and SN2 treatments significantly reduced pro-inflammatory markers IL-1β and IL-6 gene expression at day 1 post-MI (inflammatory phase). At day 7 post-MI (resolution phase), SN1/SN2 treatments continued to limit local inflammation, while mitigating fibrotic remodeling by reducing CCN2, α-SMA, and key extracellular matrix proteins. Conclusions: Together, these findings suggest that while N1-derived mediators promote a pro-inflammatory fibroblast phenotype in vitro, factors secreted by both N1 and N2 support a more balanced reparative response in vivo, by limiting local inflammation and potentially mitigating adverse remodeling post-MI.