Search Results (127)

Background/Objectives: The ongoing evolution of SARS-CoV-2 has highlighted the limitations of parenteral vaccines in preventing viral transmission, largely due to their failure to elicit robust mucosal immunity. Methods: Here, we evaluated an intranasal (IN) vaccine formulation consisting of recombinant receptor-binding domain (RBD) adsorbed onto human probiotic Bacillus subtilis DG101 spores. Results: In BALB/c mice, IN spore-RBD immunization induced strong systemic and mucosal humoral responses, including elevated specific IgG, IgM, and IgA levels in serum, bronchoalveolar lavage fluid (BALF), nasal-associated lymphoid tissue (NALT), and saliva. It further promoted mucosal B cell and T cell memory, along with a Th1/Tc1-skewed T cell response, characterized by increased IFN-γ-expressing CD4⁺ and CD8⁺ T cells in the lungs. Conclusions: All in all, these findings highlight the potential of intranasal vaccines adjuvanted with probiotic B. subtilis spores in inducing sterilizing immunity and limiting SARS-CoV-2 transmission. Full article

Biodegradable and bio-based polymers, such as starch and gelatin, are emerging as an important alternative to the use of conventional polymers. In this work, different proportions (1/1, 1/1.5, 1/2, and 1/2.5) of these bio-based polymers will be investigated, with the primary objective of considering their strong moisture dependence as an advantage instead of a problem, as commonly considered. For this interesting challenge, the humidity-activated shape memory effect has been studied in both neat and plasticized starch. Additionally, for the first time, to the best of our knowledge, the shape-memory behavior activated by humidity in gelatin, as well as in starch/gelatin blends, is reported. In all cases, starch, gelatin, and their plasticized blends show excellent values in terms of strain fixity ratio, obtaining values of about 100% in all cases, and strain recovery ratio, with values higher than 90% for the samples studied. Moreover, considering their potential application as food packaging, mechanical response, wettability, water permeability, water uptake rate, and roughness is also studied in this work, taking into account the effect of the different amounts of gelatin on the final behavior of the materials. Full article

Background and Clinical Significance: Altered pain perception is a diagnostic challenge for patients with a history of trauma and substance use. Familial dysautonomia (Riley-Day syndrome) may further complicate the sensory profiles. Case Presentation: We describe a male in his late twenties, originally from Central America, with a history of severe childhood trauma and chronic cannabis use, who reported diminished pain perception despite multiple injuries. Despite the absence of nociceptive pain (nociceptive hypoesthesia), abnormal sensations, such as tingling and itching (paresthesia), and occasionally unpleasant burning sensations (dysesthesia) were common symptoms in this case. Diagnosis: Clinical suspicion of familial dysautonomia was raised based on altered pain perception and minor autonomic signs. However, no genetic testing or neurological evaluation was performed. Psychological assessment revealed high levels of neuroticism, depression, and maladaptive coping. The Central Sensitization Inventory (CSI) and the Symptom Severity Scale (SS) further supported the presence of psychological symptoms suggestive of possible central sensitization. Outcome: Functional improvement was observed after a reduction in substance use and implementation of self-directed physical and cognitive rehabilitation. No standardized follow-up or formal interventions were recorded. Conclusions: This case illustrates the complexity of pain modulation in trauma-affected individuals and emphasizes the need for an integrative, interdisciplinary evaluation of atypical pain presentations. Full article

Mitochondria play a crucial role in oxidative stress control and reactive oxygen species (ROS) generation, impacting many cellular processes. Dysregulated mitochondria are linked to diseases such as colorectal cancer (CRC), known for its aggressiveness. Since ROS plays a role in tumor growth and metastasis, there is considerable interest in developing therapies that target these reactives. This study investigates the effects of some active substances from the micro-immunotherapy (MI) medicine 2LMIREG^® on mitochondrial metabolism parameters in two CRC-derived cell lines. HT-29 and the metastasis-derived SW620 cell lines, which heavily rely on ROS for proliferation, were used to evaluate the effects of the tested active substances. Cellular viability and various mitochondrial metabolism parameters were measured: ROS production, mitochondrial mass index, and mitochondrial DNA levels. In both cell lines, the tested MI formulation reduced cellular viability as well as ROS production compared to the vehicle used as a control. The treatment also appeared to increase the mitochondrial mass index without affecting mitochondrial DNA levels in the two CRC models. Altogether, these preliminary results report for the first time the mitochondria-related effects of some actives from 2LMIREG^® in two CRC cell models and open perspectives for further in-depth metabolism-based studies. Full article

The field of reconstructive surgery faces significant challenges in addressing limb loss and disfigurement, with current organ preservation methods limited by short storage times. Decellularization offers a promising solution for generating engineered alternatives for reconstructive surgery by removing cellular material while preserving the extracellular matrix (ECM) and providing scaffolds for tissue regeneration. In this study, we developed a robust protocol for decellularizing whole digits from long-term freezer storage, achieving the successful removal of cellular material with intact ECM. Digit angiography confirmed the preservation of vascular integrity, facilitating future perfusion for recellularization. Quantitative analysis revealed significantly lower DNA content in decellularized tissues, indicating effective decellularization. Furthermore, extracellular matrix analysis showed the preservation of collagen, elastin, and glycosaminoglycans (GAGs) contents. Histological examination confirmed the reduction in cellularity and maintenance of tissue architecture in decellularized digits. Mechanical strength testing of decellularized digit tendons proved consistent with that of native digits. Our findings highlight the potential of decellularized digits as versatile platforms for tissue engineering and regenerative medicine. Moving forward, further optimization of protocols and collaborative efforts are essential for translating these findings into clinical practice, offering innovative solutions for reconstructive surgery and limb transplantation. Full article

Metabolic reprogramming plays a crucial role in cancer biology and the mechanisms underlying its regulation represent a promising study area. In this regard, the discovery of non-coding RNAs opened a new regulatory landscape, which is in the early stages of investigation. Using a differential expression model of HOTAIR, we evaluated the expression level of metabolic enzymes, as well as the metabolites produced by glycolysis and glutaminolysis. Our results demonstrated the regulatory effect of HOTAIR on the expression of glycolysis and glutaminolysis enzymes in colorectal cancer cells. Specifically, through the overexpression and inhibition of HOTAIR, we determined its influence on the expression of the enzymes PFKFB4, PGK1, LDHA, SLC1A5, GLUD1, and GOT1, which had a direct impact on lactate and glutamate production. These findings indicate that HOTAIR plays a significant role in producing “oncometabolites” essential to maintaining the bioenergetics and biomass necessary for tumor cell survival by regulating glycolysis and glutaminolysis. Full article

Background: Patients with lung cancer experience higher rates of hospitalization due to their elevated mortality and associated comorbidities. Hospital admissions among oncology patients often indicate organ vulnerability and are linked to poor prognosis. This study aimed to assess the characteristics and potential prognostic factors of hospitalized lung cancer patients. Methods: We retrospectively analyzed 646 patients admitted from June 2021 to May 2022 to the Medical Oncology Service at La Paz University Hospital (Madrid, Spain). Results: During this period, 158 patients admitted had lung cancer (24.5%). The median overall survival since admission (mOSSA) was 3.3 months (95%CI: 1.86–7.74). In the univariate analysis, poorer mOSSA was associated with admission for tumor-related causes (1.33 vs. 7.30 months, p < 0.001), ECOG ≥ 2 (2.43 vs. 8.50 months, p < 0.001), NLR ≥ 6 (1.87 vs. 7.40 months), PNI ≤ 40 (1.67 vs. 4.97 months), and LDH ≥ 210 (2.27 vs. 7.87 months, p = 0.044). In the multivariate analysis, independent prognostic factors included admission for tumor-related causes (p = 0.032, aHR 1.81, 95%CI: 1.05–3.11) and ECOG ≥ 2 (p = 0.041, aHR 1.80, 95%CI: 1.03–3.16). Conclusions: Hospital admission for lung cancer is a poor prognostic event, particularly when associated with tumor-related causes or a decline in performance status. Full article

Background: In today’s society, low levels of physical activity are observed in the child and adolescent population, which can cause numerous pathologies, such as obesity and mental health problems. Objective: This article aims to compile all the contexts and scenarios where it is possible to increase the levels of daily physical activity of children and young people, and which have significant scientific support. Method. To do so, a literature review was carried out examining four key contexts for intervention: school, extracurricular, family, and socio-community. Results: The results indicate that the school context, with strategies such as physical education classes and active breaks, is crucial but insufficient on its own, so it is essential to complement it with interventions in extracurricular, family, and socio-community environments. The involvement of families, access to adequate infrastructure such as parks and green areas, and the responsible use of technology, including active video games and the role of influencers on social networks, are presented as key elements to combat a sedentary lifestyle. Conclusions: It is important to highlight the importance of establishing socio-educational programs that adopt a comprehensive approach to promote physical activity in children and youth, highlighting the scientific evidence that supports the effectiveness of intervening in multiple scenarios. This review concludes that a coordinated approach between different actors (schools, families, communities) is necessary to ensure that children and youth reach adequate levels of physical activity, which not only improves their physical health, but also their mental well-being and cognitive development. Full article

Nowadays, plastic contamination worldwide is a concerning reality that can be addressed with appropriate society education as well as looking for innovative polymeric alternatives based on the reuse of waste and recycling with a circular economy point of view, thus taking into consideration that a future world without plastic is quite impossible to conceive. In this regard, in this review, we focus on sustainable polymeric materials, biodegradable and bio-based polymers, additives, and micro/nanoparticles to be used to obtain new environmentally friendly polymeric-based materials. Although biodegradable polymers possess poorer overall properties than traditional ones, they have gained a huge interest in many industrial sectors due to their inherent biodegradability in natural environments. Therefore, several strategies have been proposed to improve their properties and extend their industrial applications. Blending strategies, as well as the development of composites and nanocomposites, have shown promising perspectives for improving their performances, emphasizing biopolymeric blend formulations and bio-based micro and nanoparticles to produce fully sustainable polymeric-based materials. The Review also summarizes recent developments in polymeric blends, composites, and nanocomposite plasticization, with a particular focus on naturally derived plasticizers and their chemical modifications to increase their compatibility with the polymeric matrices. The current state of the art of the most important bio-based and biodegradable polymers is also reviewed, mainly focusing on their synthesis and processing methods scalable to the industrial sector, such as melt and solution blending approaches like melt-extrusion, injection molding, film forming as well as solution electrospinning, among others, without neglecting their degradation processes. Full article

Background/Objectives: Previous preclinical studies have shown that desflurane might have the most significant cardioprotective effect of all volatile anesthetics. However, data regarding the cardioprotective effects of desflurane versus sevoflurane are lacking. Therefore, we evaluated the effect of the maintenance of anesthesia using desflurane versus sevoflurane on the postoperative maximum concentrations of cardiac biomarkers in older adults undergoing low- to moderate-risk noncardiac surgery. Methods: In this secondary analysis of a prospective randomized trial, we included all 190 older adults undergoing low- to moderate-risk noncardiac surgery. Patients were randomized to receive desflurane or sevoflurane for the maintenance of anesthesia. We administered desflurane or sevoflurane, aiming at a BIS value of 50 ± 5. The cardiac-specific biomarkers included troponin T, NT-proBNP, and copeptin, which were measured preoperatively, within one hour after surgery, and on the second postoperative day. Results: There were no significant differences between the desflurane and sevoflurane groups in the postoperative maximum concentrations of troponin T (11 ng.L⁻¹ [8; 16] versus 13 ng.L⁻¹ [9; 18]; p = 0.595), NT-proBNP (196 pg.mL⁻¹ [90; 686] versus 253 pg.mL⁻¹ [134; 499]; p = 0.288), or copeptin (19 pmol.L⁻¹ [7; 58] versus 12 pmol.L⁻¹ [6; 41]; p = 0.096). We also observed no significant differences in the troponin T, NT-proBNP, or copeptin concentrations between the desflurane and sevoflurane groups at any measured timepoint (all p > 0.05). Conclusions: In contrast to preclinical studies, we did not observe a significant difference in the postoperative maximum concentrations of cardiac biomarkers. It seems likely that desflurane does not exert significant clinical meaningful cardioprotective effects in older adults. Thus, our results do not support the use of desflurane in patients undergoing low- to moderate-risk noncardiac surgery. Full article

SARS-CoV-2 antibody kinetics based on immunologic history is not fully understood. We analyzed anti-spike and anti-nucleocapsid antibody responses following acute infection in a cohort of Indigenous persons. The models of peak concentrations and decay rates estimated that one year after infection, participants would serorevert for anti-nucleocapsid antibodies and remain seropositive for anti-spike antibodies. The peak anti-spike concentrations were higher for individuals vaccinated prior to infection, but the decay rates were similar across immunologic status groups. Children had significantly lower peak anti-spike concentrations than adults. This study affirms the importance of continued vaccination to maintain high levels of immunity in the face of waning immunity. Full article

Tonsillectomy is a common surgical procedure but carries a high risk of readmission for secondary bleeding and pain. This study evaluated the feasibility and effectiveness of using the hemostatic self-assembling peptide hydrogel RADA16 (PuraBond, 3-D Matrix SAS; Caluire et Cuire, France) to control bleeding from the tonsillectomy wound bed. Readmission/re-operation rates were compared between a prospective case series of 21 primarily adult tonsillectomy patients treated with topical RADA16 and an untreated historical Control group of 164 patients who underwent tonsillectomy by 10 surgeons at a single tertiary hospital in the UK between March 2019 and June 2022. Cumulative readmission rates for any reason were 2-fold elevated in Control subjects (18.9%; n = 31/164 subjects) compared to patients treated intra-operatively with RADA16 hemostatic hydrogel (9.5%; n = 2/21) (p = 0.378). Readmission rates for postoperative bleeding were 3-fold higher in Controls (14.6%; n = 24/164 subjects) than in the RADA16-treated group (4.8%; n = 1/21) (p = 0.317). A similar rate of retreatment for pain was recorded in the Control (4.3%; n = 7/164) and RADA16 (4.8%; n = 1/21) groups (p = 0.999). Two Control subjects (1.2%) required re-operation for recalcitrant bleeding; no RADA16 subject (0.0%) required re-operation for any reason. No device-related adverse events occurred in the RADA16 group. Surgeons were pleased with the easy learning curve and technical feasibility associated with intra-operatively administering RADA16 hemostatic hydrogel. Intra-operative hemostasis using RADA16 peptide hydrogel was straightforward and was associated with a trend of 3-fold lower rates of readmission for postoperative bleeding events than untreated Control subjects. Full article

The endothelium is a cell monolayer that lines vessels and separates tissues from blood flow. Endothelial cells (ECs) have a multitude of functions, including regulating blood flow and systemic perfusion through changes in vessel diameter. When an injury occurs, the endothelium is affected by altering its functions and structure, which leads to endothelial dysfunction, a characteristic of many vascular diseases. Understanding the role that the endothelium plays in pulmonary vascular and cardiopulmonary diseases, and exploring new therapeutic strategies is of utmost importance to advance clinically. Currently, there are several treatments able to improve patients’ quality of life, however, none are effective nor curative. This review examines the critical role of the endothelium in the pulmonary vasculature, investigating the alterations that occur in ECs and their consequences for blood vessels and potential molecular targets to regulate its alterations. Additionally, we delve into promising non-pharmacological therapeutic strategies, such as exercise and diet. The significance of the endothelium in cardiopulmonary disorders is increasingly being recognized, making ECs a relevant target for novel therapies aimed at preserving their functional and structural integrity. Full article

Introduction: The vertebral cartilage endplate (CEP), crucial for intervertebral disc health, is prone to degeneration linked to chronic low back pain, disc degeneration, and Modic changes (MC). While it is known that disc cells express toll-like receptors (TLRs) that recognize pathogen- and damage-associated molecular patterns (PAMPs and DAMPs), it is unclear if CEP cells (CEPCs) share this trait. The CEP has a higher cell density than the disc, making CEPCs an important contributor. This study aimed to identify TLRs on CEPCs and their role in pro-inflammatory and catabolic gene expression. Methods: Gene expression of TLR1–10 was measured in human CEPs and expanded CEPCs using quantitative polymerase chain reaction. Additionally, surface TLR expression was measured in CEPs grouped into non-MC and MC. CEPCs were stimulated with tumor necrosis factor alpha, interleukin 1 beta, small-molecule TLR agonists, or the 30 kDa N-terminal fibronectin fragment. TLR2 signaling was inhibited with TL2-C29, and TLR2 protein expression was measured with flow cytometry. Results: Ex vivo analysis found all 10 TLRs expressed, while cultured CEPCs lost TLR8 and TLR9 expression. TLR2 expression was significantly increased in MC1 CEPCs, and its expression increased significantly after pro-inflammatory stimulation. Stimulation of the TLR2/6 heterodimer upregulated TLR2 protein expression. The TLR2/1 and TLR2/6 ligands upregulated pro-inflammatory genes and matrix metalloproteases (MMP1, MMP3, and MMP13), and TLR2 inhibition inhibited their upregulation. Endplate resorptive capacity of TLR2 activation was confirmed in a CEP explant model. Conclusions: The expression of TLR1–10 in CEPCs suggests that the CEP is susceptible to PAMP and DAMP stimulation. Enhanced TLR2 expression in MC1, and generally in CEPCs under inflammatory conditions, has pro-inflammatory and pro-catabolic effects, suggesting a potential role in disc degeneration and MC. Full article

Para-hydroxycinnamic acid (pHCA) is one of the most abundant naturally occurring hydroxycinnamic acids, a class of chemistries known for their antioxidant properties. In this study, we evaluated the impact of pHCA on different parameters of skin aging in in vitro skin models after H₂O₂ and UV exposure. These parameters include keratinocyte senescence and differentiation, inflammation, and energy metabolism, as well as the underlying molecular mechanisms. Here we demonstrate that pHCA prevents oxidative stress-induced premature senescence of human primary keratinocytes in both 2D and 3D skin models, while improving clonogenicity in 2D. As aging is linked to inflammation, referred to as inflammaging, we analyzed the release of IL-6, IL-8, and PGE₂, known to be associated with senescence. All of them were downregulated by pHCA in both normal and oxidative stress conditions. Mechanistically, DNA damage induced by oxidative stress is prevented by pHCA, while pHCA also exerts a positive effect on the mitochondrial and glycolytic functions under stress. Altogether, these results highlight the protective effects of pHCA against inflammaging, and importantly, help to elucidate its potential mechanisms of action. Full article