Medicine and Pharmacology

Abstract: Objective: To study the effect of weight loss on the levels of vaspin, insulin, lipid profile and anthropometric indices in obese females participating in a low-energy dietary regimen combined with aerobic exercise. Materials and methods: This prospective observational study included 256 adult females aged (20-50) years were divided into 192 obese females with BMI ≥30 kg/m² and 64 normal weight females, with BMI 18.5-24.9 kg/m² as obese and control group respectively. The obese females were subgroups based on duration of dietary regimen as: Group I (3 months), Group II (6 months), and Group III (> 6 months). Each group consisted of 64 obese females and followed a low-calorie diet of 1200 to 1500 calories/day, combined with aerobic exercise training for 30 min/day all over the study period. Body mass index and waist circumference were measured post-weight loss. Serum vaspin, insulin, glucose levels, and lipid profiles were measured and analyzed statistically. Results: Baseline comparison revealed that body weight, waist circumference, BMI, vaspin, insulin, glucose, triglycerides, total cholesterol, and LDL of obese group were significantly increased compared to controls (P ≤ 0.05). Low-energy diet and aerobic exercise led to significant decrease in body weight, waist circumference, BMI, vaspin, insulin, glucose, especially with longer period of dietary regimen. Lipid profile showed improvement attitude but without statistical significance. BMI was positively correlated with most studied parameters and negatively correlated with HDL. Conclusions: Low-calorie diet accompanied with aerobic exercise were associated with body mass index, vaspin, insulin, and lipid profile level. Dieting and weight reduction, especially in longer periods, particularly for six months or more than six months, appear to normalize these parameters toward control values and improve metabolic status.

Abstract: Objective: Thyroid cartilage calcification and glucose metabolism may vary with age and gender. This study aimed to investigate the role of [18F]-sodium fluoride ([18F]NaF) and 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) PET/CT for the evaluation of physiological molecular calcification and glucose metabolism of thyroid cartilage with age. Methods: This retrospective study analyzed [18F]NaF and [¹⁸F]FDG PET/CT images from the CAMONA study (NCT01724749). Regions of interest were placed around the thyroid cartilage on CT images using OsiriX software. The mean standardized uptake value (SUVmean) was measured for [¹⁸F]NaF and [¹⁸F]FDG PET/CT images. Pearson correlation coefficients were calculated to evaluate the effects of aging on the uptake of [¹⁸F]NaF and ^[18F]FDG in the thyroid cartilage. Results: A total of 127 healthy subjects (65 females and 62 males) with a mean age of 48.46±14.13 (range 21–75) years for [¹⁸F]NaF PET/CT and a total of 114 healthy subjects (52 females and 63 males) with a mean age of 49.05±14.29 (range 21–75) years for [¹⁸F]FDG PET/CT were included. A significant positive correlation was observed between age and SUVmean of [¹⁸F]NaF in the thyroid cartilage (r=0.18, p=0.04). This result indicates that molecular calcification of this cartilage increases with aging. However, the correlation between age and SUVmean of [¹⁸F]FDG in the thyroid cartilage was not statistically significant (r=-0.09 p=0.31). Conclusion: This study presents a novel methodology for the determination of molecular calcification and glucose metabolism of laryngeal cartilage using [¹⁸F]NaF and [¹⁸F]FDG PET/CT. Molecular calcification of thyroid cartilage was found to increase with age, whereas glucose metabolism did not show a statistically significant correlation with age.

Abstract: The heel-strike (HS) paradigm of human gait originates from 19th-century chronophotographic studies conducted on Georges Demeny, a gymnasium instructor whose performed, exaggerated gait was never representative of natural locomotion. A compounding martial bias further normalised HS through military marching drill. A multi-disciplinary convergent argument analysis is conducted, integrating philological, zoological, anatomical, biomechanical, neurological and socioeconomic lines of evidence. All seven lines of argument support a forefoot-first model in which the centre of mass (CoM) leads the movement, stabilisers control equilibrium proactively, and the Triceps surae works in continuous eccentric mode---its natural functional state. Heel-strike generates impact forces up to 700 N with an ascending braking vector, under-recruits Gluteus maximus, progressively impoverishes plantar mechanoreceptors, and transmits repeated microtraumatic impulses up to the brain. Natural human gait is organised around forefoot contact, progressive CoM advance, and continuous eccentric stabiliser activity. The proposed model rediscovers lightness: a dance with gravity rather than a war against it. The HS paradigm is a culturally conditioned artefact with measurable pathological consequences.

Abstract: Traumatic tracheal injuries and congenital defects can be life threatening. Regenerating the trachea through tissue engineered scaffolds has emerged as an innovative alternative to traditional therapies. At present time, challenges in tracheal regeneration preclude clinical adoption, such as revascularization and promotion of favorable paracrine and immune signaling responses. This review summarizes current advances in tracheal regeneration and highlights key biological and engineering barriers to address to achieve functional tracheal regeneration.

Abstract: Background: The expanding interest of chatbots within the medical domain underscores the imperative for a comprehensive understanding of their capabilities and limitations, particularly in the context of anatomical education. Chatbots possess the potential to comprehend intricate anatomical concepts, deliver both advanced and contextually relevant information, and could serve as a valuable resource for medical students and educators. This study aimed to evaluate the proficiency and constraints of chatbots in the domain of neuroanatomy. Methods: We developed 30 questions and administered them to ChatGPT-4, Google Gemini, Microsoft Copilot, and Perplexity.ai, in their open versions. Questions were collaboratively constructed by the research team, selected through a semi-randomized process within the domain of neuroanatomy. Chatbots' responses were evaluated in a blinded manner for validity and appropriateness, utilizing a 5-point Likert scale. Results: The optimal performance was exhibited by ChatGPT-4 and Perplexity.ai, which achieved scores of 4.6 ± 0.5 and 4.5 ± 0.5, respectively. Microsoft Copilot (4.4 ± 0.5) and Google Gemini (4.1 ± 1.0) followed. The least successful performance was observed in the task of generating a neuroanatomical structure: only Microsoft Copilot attempted to fulfill the request, albeit with a dramatically flawed outcome. Conversely, Google Gemini and Perplexity.ai provided web links to anatomical illustrations. Conclusions: Despite technological advancements, AI models have not yet reached a level of sophistication sufficient to entirely supplant the role of educators or facilitators in a neuroanatomy course; however, they can serve as valuable adjunct tools for medical educators and students when utilized with careful consideration.

Abstract: The human microbiota is a diverse and dynamic ecosystem of microorganisms that inhabit the gastrointestinal tract and other body sites, playing a central role in host physiology. Microbial composition and density vary along the gastrointestinal tract, with the oral cavity and colon representing regions of highest diversity and microbial load, respectively. Beyond bacteria, gut virome and archaeome contribute to ecosystem stability and metabolic cooperation. The microbiota performs essential physiological functions, including maintenance of the intestinal barrier, modulation of the immune system, fermentation of dietary components into short-chain fatty acids (SCFAs), vitamin biosynthesis, and regulation of systemic metabolic and neuroendocrine pathways. Host–microbiota communication is mediated by microbial metabolites, pattern recognition receptors, immune cells, and neuroimmune interactions involving the enteric nervous system, forming the basis of the gut–brain, gut–liver, and other organ axes. Dysbiosis, caused by stress, aging, antibiotics, or an unhealthy diet, disrupts these interactions, contributing to inflammatory, metabolic, and neurodegenerative disorders. Environmental factors, including diet, physical activity, and sleep, profoundly shaped microbial composition and functional output. Diets rich in fiber, plant-based foods, and Mediterranean patterns promote microbial diversity and SCFA production, whereas Western diets predispose dysbiosis and systemic inflammation. Understanding the mechanisms by which microbiota influences host physiology provides opportunities for targeted interventions, including probiotics, prebiotics, and lifestyle modifications, aimed at restoring microbial balance and improving health outcomes. This review integrates current knowledge on the composition, function, and modulators of the human microbiota, emphasizing its central role in maintaining intestinal and systemic homeostasis across the lifespan.

Abstract: Background/Objectives: Wound healing is a complex biological process involving co-ordinated interactions among inflammatory cells, growth factors, extracellular matrix components, and resident tissue cells. Despite significant advances in experimental research, translation of these findings into clinical practice remains limited, partly due to the lack of reproducible and ethically accessible human wound models. Pilonidal disease, a chronic inflammatory condition of the sacrococcygeal region, is frequently treated by surgical excision with healing by secondary intention. The resulting open wound provides a unique opportunity to study the natural progression of human tissue repair. Methods: This narrative review examines current knowledge on wound-healing phys-iology, commonly used experimental wound models, and clinical studies related to pi-lonidal disease. Evidence from experimental, translational, and clinical literature was evaluated to explore the potential of open pilonidal excision wounds as a standardized human model for wound-healing research. Results: Following open excision, healing typically occurs within 4–10 weeks through the classical phases of inflammation, pro-liferation, and tissue remodeling. During this period, the wound remains externally accessible, allowing repeated clinical observation and serial collection of tissue samples, wound fluid, and exudate. This accessibility facilitates investigation of key biological processes, including angiogenesis, fibroblast proliferation, epithelial migration, cyto-kine signaling, and extracellular matrix remodeling. Compared with in vitro systems and animal models, the open pilonidal wound offers direct insight into human wound biology under clinically relevant conditions. Conclusions: Open pilonidal excision wounds constitute a reproducible and ethically feasible in vivo human model for translational wound-healing research. This model may support biomarker discovery and contribute to the development of new therapeutic strategies for impaired healing and chronic wounds

Abstract: Aging is a chronic, destructive process characterized by the progressive breakdown of the body, leading to a loss of control over homeostasis. Scientific evidence indicates that energy dysmetabolism, particularly the loss of regulation in glucose-dependent metabolic processes, significantly contributes to the aging process. In healthy individuals, glucose levels are tightly regulated, enabling optimal adaptation to the body's physiological demands. However, as glucose metabolism declines with age, it leads to pathological changes in cellular and tissue function, which in turn results in chronic inflammation that can further accelerate aging. In this narrative review, I examine the complex and multifaceted aspects of aging, which are driven by age-related and irreversible changes in cellular and tissue structure and function. These alterations directly affect brain function, the primary regulator of vital bodily processes. The age-related structural and functional changes observed in long-lived cells, especially neurons, cardiomyocytes, and osteocytes, significantly impact both the quality and longevity of life. Research aimed at improving glucose metabolism by supplementing nicotinamide adenine dinucleotide (NAD) precursors shows promise for enhancing both the quality and length of life.

Abstract: Anatomical variants are observed on paired body sides, yet many prevalence studies—particularly those based on osteological collections—report only right- and left-side frequencies without specifying whether findings occur bilaterally in the same individual. In such cases, the individual-level left–right structure is unobserved. Consequently, inference on laterality and bilateralism cannot be based on the reported data alone and must rely on explicit assumptions about within-individual dependence.We study this problem in the context of anatomic prevalence data, although the framework applies more broadly to paired binary outcomes. We parameterize the admissible joint distributions using a feasibility-based dependence index, λ, spanning the full range from independence to maximal feasible concordance implied by the marginal prevalences. Within this framework, we examine two complementary estimands: the paired odds ratio for laterality and bilateral prevalence.Analytic results and Monte Carlo simulations show that bilateral prevalence varies linearly and remains stable across the admissible dependence range, whereas the paired odds ratio exhibits intrinsic boundary instability as dependence approaches its feasible maximum due to vanishing discordant counts. Uncertainty-propagation analyses further indicate that laterality inference is robust to moderate misspecification of the dependence assumption. These results demonstrate that unobserved within-subject dependence is a structural inferential issue in paired binary meta-analysis and motivate feasibility-based sensitivity analysis when only marginal data are available.

Abstract: Ischemic heart disease remains the most significant cause of morbidity and mortality worldwide. Althoughconventional therapies such as β-blockers, ACE inhibitors, statins, and percutaneous coronary intervention havereduced mortality in industrialized nations, progress has plateaued, and global ischemic burden continues to rise.Renewed scientific attention has turned to canonical cardioprotective signaling pathways with a level of molecularprecision not previously feasible. Parallel advances in exercise biology and mesenchymal stem-cell derived exosome(MSC-EXO) research suggest an opportunity for integrative cardioprotection. Exercise, once understood primarilyin descriptive physiologic terms, is now recognized as a complex molecular stimulus that can activateredox-sensitive kinases, autophagy regulators, and metabolic remodeling pathways. New state-of-the-artinvestigations have gone towards decoding this “exercise secretome” and developing tools to modulate thesechemical cascades. Multiple experimental studies report that MSC-derived exosomes function as biologically activeparacrine vectors that deliver regulatory microRNAs and proteins to recipient cells and promote angiogenesis,suppress apoptosis, and support mitochondrial function. This narrative review assesses the effectiveness ofinterventions on canonical pathways such as ERK and AKT/mTOR on ISO-induced ischemic injury models to theheart based on recent animal and human studies. Supporting literature on stem cell biology, exosome deliverystrategies, and translational barriers is discussed to create an integrated framework that reinforces and sustainsreparative signaling in ISO-induced ischemic environments. Together, these two rapidly evolving fields, exercisebiology and MSC-ECO, may define the next frontier in regenerative ischemic cardiomyopathy by harnessing innaterepair pathways and bioengineered tools to potentiate the crosstalk among metabolic, kinase, and paracrine survivalcircuits.

Abstract: The centrosome, long recognized as the primary microtubule-organizing center (MTOC) of animal cells, is re-examined through the lens of information theory and systems biology. This preprint proposes a unifying hypothesis: the mother centriole within the centrosome acts as a non-genetic cellular ledger, a stable structural repository that accumulates molecular records of a cell’s replicative history and environmental exposures. These records—comprising specific post-translational modification (PTM) signatures, retained proteins, and structural alterations—are subsequently “read” by the cell to inform critical decisions regarding proliferation, differentiation, senescence, and apoptosis. We synthesize evidence from cell biology, gerontology, and evolutionary biology to construct the “Centrosomal Ledger Model.” This model positions the centriole not as a passive cytoskeletal component but as an active, heritable information-processing node that integrates temporal data across scales—from circadian rhythms to organismal aging. We detail the molecular mechanisms of information encoding (e.g., tubulin polyglutamylation, oxidative marks) and decoding (via ciliary signaling, proteostatic feedback, and mechanical transduction). The model’s implications challenge genetic determinism by highlighting structural inheritance, provides a material basis for cellular age, and offers novel, falsifiable avenues for experimental interrogation in aging and cancer research. Crucially, it suggests that modulating the “read-write” cycle of the centrosomal ledger could represent a new frontier in regenerative medicine.

Abstract: Although self-administered antigen tests are widely available, anatomical knowledge of nasal anatomy in the general population is limited. Cerebrospinal fluid leakage has been reported in multiple cases following damage to the roof of the nasal cavity due to accidental penetration of the cribriform plate of the ethmoid bone. Methods: Images of anatomical prosections used for teaching in the Dissection Room of the Faculty of Medicine of the University of Barcelona were obtained to illustrate the viable horizontal pathway to the nasopharynx through the inferior meatus, below the inferior turbinate. Screenshots from publicly available videos produced by the author demonstrating swab insertion were analyzed to measure the final insertion angle using 3D software. Publicly available instructions for patients included with authorized antigen tests in Spain were reviewed. Results: Antigen tests available in Spain in 2025 recommended a predominantly vertical swab insertion. However, successful horizontal insertion in the inferior meatus towards the nasopharynx can be achieved with a slight vertical angle of 7–9°. A schematic illustration for free use is provided. Conclusion: Swab instructions should be revised to emphasize an insertion perpendicular to the face in order to access the inferior meatus safely and reduce the risk of injury to the ethmoidal cells.

Abstract: Hypoxic pulmonary vasoconstriction (HPV) is a rapid and reversible constrictor response of the pulmonary vasculature, and especially its small muscular precapillary arteries, which is initiated by episodes of local alveolar hypoxia. Acting as a protective homeostatic vasomotor mechanism, HPV enables maximal gas exchange by diverting blood from poorly ventilated alveoli in to those rich in oxygen, thereby optimizing oxygen uptake and the ventilation-perfusion (V/Q) ratio so as to maintain the arterial oxygen partial pressure (P_aO₂) within the physiological range. HPV is an intrinsic mechanism of pulmonary artery smooth muscle cells (PASMC), and requires an O₂ sensor which acts through mediator(s) to trigger effector mechanisms within these cells to evoke constriction. Whereas HPV effector mechanisms are reasonably well-defined, the nature of the O₂ sensor and mediators remain in dispute. The three most comprehensive models of O2 sensing in HPV share a focus on the concept that hypoxia activates effector mechanisms by inducing a change in the PASMC cytoplasmic redox state. According to the Redox Theory, first proposed by Kenneth Weir and Stephen Archer in 1995, hypoxia inhibits mitochondrial production of reactive oxygen species (ROS), thereby causing the cytoplasm to become more reduced. This inhibits ongoing vasorelaxation maintained by the opening of voltage-gated K+ channels. In contrast, according to the Mitochondrial ROS hypothesis, introduced by Paul Schumacker and Naveen Chandel in 2001, hypoxia increases mitochondrial ROS production, causing an oxidizing shift in the cytoplasmic redox poise which activate several vasoconstricting pathways. In a third scenario, developed by Michael Wolin and Sachin Gupte, hypoxia evokes contraction by causing a fall in H2O2 production by NADPH oxidase, and by activating the pentose phosphate pathway. These effects inhibit basal vasorelaxation maintained by the guanylate cyclase and protein kinase G and also stimulate vasoconstricting mechanisms. In this comprehensive review, we summarize the key studies contributing to the development of these proposals and then subject the evidence supporting them to critical appraisal, based in part on how well they accord with the wider literature and recent developments in our understanding of how cells shape and deploy redox mechanisms in order to regulate cell function.

Abstract: Minimally invasive facial procedures are widely performed in clinical medicine but re-main associated with severe complications such as necrosis or blindness, often resulting from insufficient anatomical understanding and limited procedural training. To address these challenges, this study developed an anatomically accurate clinical simulator for fa-cial injection training. A three-dimensional polygonal facial model was constructed using standardized anatomical datasets reflecting skeletal dimensions, soft tissue characteris-tics and the average arterial distribution of East Asian faces. This model was integrated into simulation software connected to a facial silicone dummy with realistic tissue texture and an optical tracking system providing sub-millimeter precision. Each anatomical structure, including muscles, vessels and nerves, was digitally annotated and linked to interactive visualization tools. During training, the simulator simultaneously reflected the real-time needle trajectory and insertion depth; when the needle tip approached a high-risk structure, such as the supraorbital artery, alerts were automatically triggered. This feedback enabled trainees to recognize unsafe injection zones and adjust their tech-nique accordingly. The system provided a realistic, repeatable and safe environment for improving anatomical comprehension and procedural accuracy. This study proposes an innovative applied simulation system that may enhance medical education and clinical safety in facial injection procedures.

Abstract: Intervertebral disc (IVD), the largest avascular structure in the human body, contains nucleus pulposus (NP) cells that generate an abundant quantity of lactate from anaerobic glycolysis as an adaptation to hypoxia. Historically, IVD lactate was viewed as a metabolic toxic byproduct necessitating clearance to maintain IVD health. This is because accumulation of lactic acid, the protonated form of lactate, acidifies the IVD microenvironment, impairs cell viability, disrupts extracellular matrix integrity, and promotes degeneration. However, recent studies discovered that lactate serves as an important IVD biofuel in a process known as lactate-dependent metabolic symbiosis in which lactate produced by NP is shuttled into cells of the neighboring annulus fibrosus (AF), and cartilage endplate (CEP) to be metabolized via the tricarboxylic acid cycle and oxidative phosphorylation to generate ATP and amino acids to maintain IVD matrix homeostasis. Additionally, lactate is found to function as a signaling molecule and epigenetic regulator in IVD: it regulates transcription via histone lactylation that modulates ferroptosis and other cell fate decisions. Lactate also modulates senescence, apoptosis, and inflammatory responses through pathways such as Phosphatidylinositol 3-kinase/Protein kinase B (PI3K/Akt) in IVD and other organs. This review synthesizes current knowledge on lactate production, transport, and clearance in the IVD along with the emerging roles of lactate in IVD health and pathophysiology. The review also provides research perspectives and directions aimed at advancing our understanding of lactate biology and evaluating its potential as a therapeutic target for treating intervertebral disc degeneration.

Abstract: Introduction: Chronic Obstructive Pulmonary Disease (COPD), a respiratory pathology primarily linked to smoking, appears to exacerbate oral health problems through systemic and local mechanisms. This study evaluates the impact of COPD on the oral health of smoking patients in an Algerian context.​Methods: A descriptive cross-sectional study was conducted from January to June 2023 at the University Hospital Center of Sidi Bel Abbès, Algeria. A total of 138 male smoking patients were included. Each participant answered a standardized questionnaire, underwent a thorough clinical oral examination, and spirometry to confirm the diagnosis of COPD (FEV/FVC < 0.7 post-bronchodilator).​Results: Out of 138 patients, 62 (44.9%) had confirmed COPD. Tooth loss was significantly more frequent among COPD patients (88.7%) than among non-COPD patients (77.6%, p = 0.03). Dental caries were also more prevalent in the COPD group (85.5%) compared to the non-COPD group (70.1%, p = 0.02). Gum disease (93.5% vs. 91.3%, p = 0.65) and bad breath (79.0% vs. 76.0%, p = 0.70) showed similar prevalences in both groups.​Conclusion: COPD is associated with a significant deterioration of oral health, particularly regarding tooth loss and dental caries. A multidisciplinary management approach involving pulmonologists and dentists is crucial to improve clinical outcomes and patient quality of life.

Abstract: The skin-to-transverse process distance (st) correlates with the skin-to-dural sac depth (d) and may be used to estimate optimal angles for perpendicular needle insertion using the formula: inverse cosine d/√(1 + d²), as outlined in free visual guides. Objective: To analyze the relationship between the transverse process and dural sac depth at lumbar levels relevant to spinal anesthesia, and to determine the range of planes where a perpendicular paramedian needle insertion is feasible when midline access is not viable. Methods: Ten ex vivo trunks were flexed using an abdominal support, and CT scans were performed. Correlations between the transverse process and dural sac depth were evaluated from L3 to S1. Perpendicular planes at the level of needle paths were examined at L3-L4 and L4-L5. Median path viability was assessed. Results: The transverse process aligned with the dorsal dural sac at L3, the posterior third at L4, and the middle zone at L5-S1. Median needle insertion was not viable in 20–30% of L4-L5 and L3-L4 levels, respectively. However, paramedian access was possible. The vertical range of viable paramedian planes was 8.7 ± 2.9 mm (L4–L5) and 7.9 ± 1.9 mm (L3–L4). Coronal reconstructions showed that the upper level of the transverse process correlates with the skin-perpendicular planes where insertion is likely to succeed. Conclusion: Many elderly spines lack viable midline paths. The superior aspect of the transverse process serves as a useful landmark for estimating dural sac depth, calculating paramedian angles, and identifying the plane for successful perpendicular needle insertion.

Abstract: The incorporation of artificial intelligence into medical pedagogy necessitates a thorough appraisal, especially within fundamental disciplines like anatomy, where accurate understanding is paramount. The efficacy of advanced AI systems, specifically Large Language Models like ChatGPT, in the acquisition and retention of specialized medical knowledge continues to be an active area of research and evaluation. This cross-sectional study was undertaken in August 2025, to evaluate the proficiency of ChatGPT in responding to multiple-choice questions within basic medical sciences, with a particular emphasis on the domain of anatomy. A compilation of 124 meticulously selected multiple choice questions from the mid-term and final examinations administered to first-year medical students, was utilized; Anatomy (28), Histology (23), Microbiology (21), Pathology (33) and Physiology (19). Strict criteria applied to ensure questions were unambiguously framed as single-best-answer items. Paper of each discipline was submitted to ChatGPT, and initial response considered definitive. Performance was scored on a binary scale and analyzed descriptively. Results revealed high accuracy, with ChatGPT answering 96% Anatomy questions correctly, 100% Histology and Physiology, Pathology 97% and Microbiology 95%, achieving an overall accuracy of 98%. The results indicate a substantial capacity for ChatGPT to serve as a valuable pedagogical resource for reinforcing knowledge and facilitating self-evaluation.

Abstract: Exposure to hypoxia may cause lung injury characterized by hydrostatic pulmonary edema (PE), inflammation and oxidative stress. Norepinephrine (NE) infusion can also induce lung injury with similar pathogenetic characteristics. The main questions of this study were (i) whether NE infusion aggravates hypoxia-induced pulmonary injury; (ii) whether inflammation and oxidative stress deteriorate the hypoxic PE; (iii) whether PE and inflammation recede after three days of normoxic recovery. Ninety-eight female rats were exposed for 72 h to normoxia or normobaric hypoxia and received infusions with NaCl or NE. Some of these animals were transferred to a three-day normoxic recovery period thereafter. We performed histological and immunohistochemical analyses of the lung, determined protein concentrations in pleural fluid (PF) and bronchoalveolar lavage fluid (BALF), and evaluated hemodynamic parameters. While inflammation and oxidative stress receded after 3 days of normoxic recovery, PE did not resolve. Increased protein concentrations in PF and BALF indicated that capillary stress failure increased even further during the normoxic recovery phase, in particular in animals that had previously received NE infusion. These results highlight the fact that inflammation does not play a causal role in the development of hypoxic PE.

Abstract: Coagulation, although primarily regulated by platelets, endothelial cells, and clotting factors, can also be influenced by molecules that are not traditionally seen as related to coagulation, including cytokines, hormones, metabolites, reactive oxygen species, acute phase reactants, and more. Here, we derive pseudoserum or clotting factor-depleted fractions from control, type II diabetes mellitus, and Long COVID platelet-poor plasma (PPP) samples, and expose them to purified, exogenous fibrinogen obtained from healthy donors. Thrombin-induced fibrin networks were then formed and visualized using light and scanning electron microscopy. The results demonstrate that pseudoserum can greatly influence the organisation, density, and ultrastructure of fibrin networks formed from purified fibrinogen, emphasizing the role of non-clotting factors in fibrin formation. Fibrin networks formed from purified fibrinogen exposed to control pseudoserum appear homogeneous, exhibiting organized architecture with few regions of unusual density or aggregates, whereas the networks formed using patient pseudoserum show disorganisation, regions of density, fibre-like strands, and anomalous aggregates. These abnormalities are also observed in patient PPP samples, suggesting that fibrin network characteristics in PPP samples are also significantly influenced by non-clotting factors and are somewhat independent of endogenous fibrinogen. The ability of pseudoserum to drive these changes, despite the absence of endogenous fibrinogen and other classical clotting factors, suggests that soluble molecules retained in pseudoserum can directly modify fibrinogen’s structural conformation and functionality, influence thrombin-mediated fibrin formation and polymerization, and/or impact Factor XIII’s crosslinking capabilities. This study provides a systems-level perspective on the influence of pseudoserum on fibrin networks and highlights the potential of serum and other clotting factor–depleted fractions to yield deeper mechanistic and diagnostic insights into coagulation.