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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.
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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.
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Cromatina , Factor de Transcripción AP-1 , Factor de Transcripción AP-1/metabolismo , Cromatina/metabolismo , Animales , Envejecimiento/metabolismo , Humanos , Elementos de Facilitación Genéticos/genética , Senescencia CelularRESUMEN
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.
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Senescencia Celular , Enfermedades Pulmonares Intersticiales , Fibrosis Pulmonar , Humanos , Senescencia Celular/inmunología , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/patología , Fibrosis Pulmonar/inmunología , Fibrosis Pulmonar/patología , Animales , Pulmón/inmunología , Pulmón/patología , InmunidadRESUMEN
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.
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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.
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Encéfalo , Linaje de la Célula , Oligodendroglía , Animales , Oligodendroglía/fisiología , Ratones , Encéfalo/citología , Encéfalo/embriología , Linaje de la Célula/fisiología , Diferenciación Celular/fisiología , Ratones Transgénicos , Vaina de Mielina/metabolismo , Vaina de Mielina/fisiologíaRESUMEN
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.
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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.
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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.
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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.
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[This corrects the article DOI: 10.1371/journal.pone.0005475.].
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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.
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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.
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The genome-organizing protein p6 of Bacillus subtilis bacteriophage φ29 plays an essential role in viral development by activating the initiation of DNA replication and participating in the early-to-late transcriptional switch. These activities require the formation of a nucleoprotein complex in which the DNA adopts a right-handed superhelix wrapping around a multimeric p6 scaffold, restraining positive supercoiling and compacting the viral genome. Due to the absence of homologous structures, prior attempts to unveil p6's structural architecture failed. Here, we employed AlphaFold2 to engineer rational p6 constructs yielding crystals for three-dimensional structure determination. Our findings reveal a novel fold adopted by p6 that sheds light on its self-association mechanism and its interaction with DNA. By means of protein-DNA docking and molecular dynamic simulations, we have generated a comprehensive structural model for the nucleoprotein complex that consistently aligns with its established biochemical and thermodynamic parameters. Besides, through analytical ultracentrifugation, we have confirmed the hydrodynamic properties of the nucleocomplex, further validating in solution our proposed model. Importantly, the disclosed structure not only provides a highly accurate explanation for previously experimental data accumulated over decades, but also enhances our holistic understanding of the structural and functional attributes of protein p6 during φ29 infection.
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Fagos de Bacillus , Bacillus subtilis , Fagos de Bacillus/genética , Fagos de Bacillus/química , Bacillus subtilis/virología , Replicación del ADN , ADN Viral/genética , Nucleoproteínas/metabolismo , Proteínas Virales/metabolismoRESUMEN
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.
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Longevidad , Receptor Toll-Like 5 , Animales , Ratones , Flagelina/metabolismo , Mucosa Intestinal/metabolismo , Longevidad/genética , Pulmón/metabolismoRESUMEN
Background and Aim: Airline pilots (APs) are often characterized by a sedentary lifestyle, predisposing them to adverse cardiometabolic consequences. In this cross-sectional study, we used transient elastography (TE) to investigate the prevalence of hepatic steatosis and fibrosis among apparently healthy APs. Materials and Methods: The study cohort consisted of 137 male APs of Caucasian descent who voluntarily underwent TE. To evaluate the extent and severity of hepatic steatosis and fibrosis, we employed established cutoff values for the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Results: Of the APs, 34 (24.8%) were diagnosed with TE-defined steatosis. Specifically, 25 APs (18.2%) exhibited mild steatosis, 6 (4.4%) moderate steatosis, and 3 (2.2%) severe steatosis. The majority of participants (80 APs or 58.4%) showed no signs of liver fibrosis based on LSM values. However, 49 APs (35.8%) were diagnosed with mild fibrosis (F1), 7 (5.1%) with significant fibrosis (F2), and one (0.7%) with advanced fibrosis (F3). None of the pilots had F4 (cirrhosis). In multivariable linear regression analysis, BMI was the sole independent predictor of both CAP (ß=0.34, p<0.001) and LSM (ß=0.41, p<0.001) values in our sample of male APs. Conclusion: TE is a straightforward and convenient non-invasive method for detecting hepatic steatosis and fibrosis in high-risk occupational groups such as APs.
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Chemotherapy often generates intratumoral senescent cancer cells that strongly modify the tumor microenvironment, favoring immunosuppression and tumor growth. We discovered, through an unbiased proteomics screen, that the immune checkpoint inhibitor programmed cell death 1 ligand 2 (PD-L2) is highly upregulated upon induction of senescence in different types of cancer cells. PD-L2 is not required for cells to undergo senescence, but it is critical for senescent cells to evade the immune system and persist intratumorally. Indeed, after chemotherapy, PD-L2-deficient senescent cancer cells are rapidly eliminated and tumors do not produce the senescence-associated chemokines CXCL1 and CXCL2. Accordingly, PD-L2-deficient pancreatic tumors fail to recruit myeloid-derived suppressor cells and undergo regression driven by CD8 T cells after chemotherapy. Finally, antibody-mediated blockade of PD-L2 strongly synergizes with chemotherapy causing remission of mammary tumors in mice. The combination of chemotherapy with anti-PD-L2 provides a therapeutic strategy that exploits vulnerabilities arising from therapy-induced senescence.
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Neoplasias Pancreáticas , Animales , Ratones , Neoplasias Pancreáticas/metabolismo , Linfocitos T CD8-positivos/patología , Tolerancia Inmunológica , Terapia de Inmunosupresión , Senescencia Celular , Microambiente TumoralRESUMEN
BACKGROUND: Vitamin B12 is an essential nutrient that is involved in numerous physiological processes, and its deficiency can lead to various complications, including neurological and haematological disorders. Some studies have suggested that vitamin B12 may have anti-inflammatory effects, but the mechanisms underlying this relationship are not yet fully understood. We investigated the relationship between circulating vitamin B12 and inflammatory markers interleukin (IL)-6 and C-reactive protein (CRP). The association of peripheral levels of vitamin B12 with IL-6 and CRP was assessed in 136 human samples from a high cardiovascular risk population. To corroborate the results from the human trial, the analysis was replicated in naturally aged mice. RESULTS: Individuals with higher serum levels of vitamin B12 showed lower concentrations of IL-6 and CRP after adjustment for potential confounders, and an inverse association was also found between serum IL-6 and vitamin B12 levels in naturally aged mice. CONCLUSION: Circulating vitamin B12 was inversely associated with IL-6 and CRP in humans and with IL-6 in mice, suggesting that it may exert an anti-inflammatory effect through modulation of these pro-inflammatory molecules. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
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Enfermedades Cardiovasculares , Deficiencia de Vitamina B 12 , Humanos , Animales , Ratones , Vitamina B 12 , Enfermedades Cardiovasculares/etiología , Interleucina-6 , Factores de Riesgo , Biomarcadores , Proteína C-Reactiva/metabolismo , Factores de Riesgo de Enfermedad Cardiaca , Antiinflamatorios , Ácido FólicoRESUMEN
Introduction Water is essential for life and is vital for almost all functions of the human body. Recent studies have shown that treating water with magnets can alter its physicochemical properties, including intracluster bonds and water-ion interactions. Magnetized water also undergoes modifications in its physicochemical characteristics, such as pH, salinity, and dissolved oxygen. While there is a significant amount of literature on the use of magnetized water in agricultural settings, research on its potential biomedical applications is still limited. Based on previous findings indicating a potential relationship between autophagy activation and hair loss reversal, a pilot study was designed to explore the effects of topically applied magnetized saline water in patients with androgenetic alopecia. The hypothesis was that the process of water magnetization, which promotes the creation of hydroxyl ions, could potentially induce hair growth through the induction of alkali-induced autophagy in the scalp. Methods We recruited 20 Caucasian men with mild-to-moderate androgenetic alopecia (Norwood-Hamilton stages II-III). Initially, we conducted a 12-week open-label study to evaluate the potential of a topical lotion containing 95% magnetized saline water (2 mL applied once daily) to increase hair count and hair mass index (HMI). Subsequently, we investigated the effect of the lotion on two autophagy markers (Beclin-1 and LC3B) in scalp biopsies from a subgroup of 10 men. Results Hair count significantly increased after 12 weeks of topical treatment with magnetized saline water (from 20.6 ± 9.8 at baseline to 32.5 ± 12.4 at 12 weeks, P < 0.001). Similarly, the mean HMI increased from 37.8 ± 11.4 at baseline to 45.1 ± 13.6 at 12 weeks (P < 0.01). At the molecular level, the topical lotion effectively increased Beclin-1 levels in scalp biopsies by 44% at 12 weeks as compared to the baseline. Similarly, LC3B levels increased by 36% from baseline to 12 weeks, indicating that the lotion effectively activated autophagy in the scalp. Conclusions After 12 weeks of topical treatment, a lotion containing magnetized saline water activated scalp autophagy and significantly increased hair count and HMI in men with mild-to-moderate androgenetic alopecia.
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Fibrogenesis is part of a normal protective response to tissue injury that can become irreversible and progressive, leading to fatal diseases. Senescent cells are a main driver of fibrotic diseases through their secretome, known as senescence-associated secretory phenotype (SASP). Here, we report that cellular senescence, and multiple types of fibrotic diseases in mice and humans are characterized by the accumulation of iron. We show that vascular and hemolytic injuries are efficient in triggering iron accumulation, which in turn can cause senescence and promote fibrosis. Notably, we find that senescent cells persistently accumulate iron, even when the surge of extracellular iron has subdued. Indeed, under normal conditions of extracellular iron, cells exposed to different types of senescence-inducing insults accumulate abundant ferritin-bound iron, mostly within lysosomes, and present high levels of labile iron, which fuels the generation of reactive oxygen species and the SASP. Finally, we demonstrate that detection of iron by magnetic resonance imaging might allow non-invasive assessment of fibrotic burden in the kidneys of mice and in patients with renal fibrosis. Our findings suggest that iron accumulation plays a central role in senescence and fibrosis, even when the initiating events may be independent of iron, and identify iron metabolism as a potential therapeutic target for senescence-associated diseases.
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Senescencia Celular , Fenotipo Secretor Asociado a la Senescencia , Humanos , Hierro , Riñón , FibrosisRESUMEN
The presence of antiphospholipid antibodies (aPLs) is associated with antiphospholipid syndrome (APS), characterized by thrombosis and obstetric morbidity. aPLs included in APS classification criteria are lupus anticoagulant, anti-cardiolipin and anti-beta-2-glycoprotein-I of IgG or IgM isotypes. Enzyme-linked immunosorbent assay is the most used diagnostic technique to determine aPLs. Recently, new automated technologies mainly based in antigen-coated beads have been developed. The aim is to compare a fluorescence enzyme immunoassay (M1) and an antigen-coated bead assay (M2) in obstetric and thrombotic APS patients. All samples from the first 1020 patients received in the Immune Service Laboratory (Hospital 12 de Octubre) during the recruitment period, without exclusions, were analysed for aPLs. The weighted kappa for both methods in all the patients was 0.39 (0.30-0.47). Agreement increased to 0.56 (0.38-0.73) in patients with autoimmune disease. Sensitivity and specificity obtained for M1 were 17.1% and 89.3%, respectively, and 12.7% and 91.4% for M2. The sensibility and specificity of IgG isotypes were higher than the IgM ones. Regarding obstetric patients, M1 obtained significant diagnostic performance and had more sensitivity 23.75 (14.95-34.58) compared to M2 12.50 (6.16-21.79). In conclusion, clinical suspicion-based method selection for aPLs should be considered. To identify obstetric APS patients, solid phase methods remain more preferable.