Search Results (31)

The zebrafish (Danio rerio) has emerged as a powerful model organism for investigating the mechanisms of post-traumatic stress disorder (PTSD), offering unique advantages in translational relevance, genetic trackability, and cost-effectiveness. As a logical continuation of our recent systematic review, this manuscript critically examines the spectrum of experimental strategies used to model PTSD in zebrafish, with a focus on the comparative efficacy and validity of acute, chronic, and complex stress paradigms. Among these, 14–15-day chronic unpredictable stress (CUS/UCS) protocols are identified as the gold standard, reliably inducing core PTSD-like phenotypes—such as anxiety-like behavior, cortisol dysregulation, and neuroinflammatory gene activation. We discuss the influence of environmental, developmental, and genetic factors on stress responses, and highlight the importance of standardized behavioral and molecular endpoints for model validation. While alternative paradigms—including acute, social, pharmacological, and predator-based models—offer mechanistic insights, their translational relevance remains limited without further refinement. We conclude by outlining future directions for zebrafish-based PTSD research, emphasizing the need for protocol harmonization, integration of multi-modal readouts, and exploration of individual variability to enhance the translational value of this model system. Full article

Background and Objectives: This is the first systematic review to focus exclusively on in vivo randomized controlled trials that compare bulk-fill and conventional incremental composite restorations in primary teeth. Our aim was to synthesize current evidence on their clinical performance, including retention, two-year survival rates, marginal integrity, and procedural efficiency. Methods: A comprehensive literature search was conducted in PubMed, Scopus, and the Elicit AI platform up to March 2025. Eligible studies were in vivo randomized controlled trials involving children aged 3–12 years with carious primary teeth, directly comparing bulk-fill and incremental composite restorations. Primary outcomes included retention rates, two-year survival, and marginal integrity, while secondary outcomes were postoperative sensitivity, secondary caries, and aesthetic outcomes. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessments using the Cochrane RoB 2.0 tool. A narrative synthesis was undertaken due to substantial heterogeneity in study design and outcome reporting. The review protocol was registered in PROSPERO (CRD420251021433). Results: Thirteen randomized controlled trials met the inclusion criteria. Both restoration techniques demonstrated high short-term retention rates (>90%) and comparable two-year survival (85–90%). Marginal integrity was generally equivalent, though incremental techniques showed modest advantages in complex cavities. Secondary outcomes were inconsistently reported, with no significant group differences. Bulk-fill restorations consistently reduced the procedural time by 2–4 min per restoration, representing a meaningful advantage in pediatric clinical settings. Conclusions: Bulk-fill composites offer a clinically effective and time-efficient alternative to incremental layering in the restoration of primary teeth. This focused synthesis addresses a gap in existing reviews by concentrating solely on primary dentition and in vivo evidence. Despite similar clinical outcomes, the time savings associated with bulk-fill techniques may enhance their utility in pediatric dentistry. Further standardized and long-term trials are warranted to confirm these findings and inform clinical guidelines. Full article

Consciousness remains one of the most critical yet least understood functions of the brain, not only in humans but also in certain highly organized animal species. In this review, we propose treating consciousness as an emergent, goal-directed informational system organized by the subjective “self” as an active system-forming factor. We present an integrative theoretical–systems framework in which subjectivity functions as system-forming factor of consciousness (SFF) throughout biological evolution. Beginning with proto-conscious invertebrates, we trace progressive elaborations of working and long-term memory, the refinement of behavioral programs, and the emergence of an internal arbiter capable of resolving competing drives. In endothermic vertebrates, subjectivity acquires distinct functional features—sensory filtering, causal reasoning, and adaptive arbitration—underpinned by increasingly complex neural architectures. This evolutionary trajectory culminates in humans, where subjectivity attains its highest level of organization through culturally mediated networks. Although the framework does not assume any specific neural substrate, it provides a testable roadmap linking evolutionary biology, information theory, and quantitative modeling. By clarifying why consciousness arose and how subjectivity shapes complex networks, this perspective also lays the groundwork for exploring possible nonbiological extensions of subjectivity. Full article

Stem-cell behavior is governed not solely by intrinsic genetic programs but by highly specialized microenvironments—or niches—that integrate structural, biochemical, and mechanical cues to regulate quiescence, self-renewal, and differentiation. This review traces the evolution of stem-cell niche biology from foundational embryological discoveries to its current role as a central determinant in tissue regeneration and disease. We describe the cellular and extracellular matrix architectures that define adult stem-cell niches across diverse organs and dissect conserved signaling axes—including Wnt, BMP, and Notch—that orchestrate lineage commitment. Emphasis is placed on how aging, inflammation, fibrosis, and metabolic stress disrupt niche function, converting supportive environments into autonomous drivers of pathology. We then examine emerging therapeutic strategies that shift the regenerative paradigm from a stem-cell-centric to a niche-centric model. These include stromal targeting (e.g., FAP inhibition), which are engineered scaffolds that replicate native niche mechanics, extracellular vesicles that deliver paracrine cues, and composite constructs that preserve endogenous cell–matrix interactions. Particular attention is given to cardiac, hematopoietic, reproductive, and neurogenic niches, where clinical failures often reflect niche misalignment rather than intrinsic stem-cell deficits. We argue that successful regenerative interventions must treat stem cells and their microenvironment as an inseparable therapeutic unit. Future advances will depend on high-resolution niche mapping, mechanobiologically informed scaffold design, and niche-targeted clinical trials. Re-programming pathological niches may unlock regenerative outcomes that surpass classical cell therapies, marking a new era of microenvironmentally integrated medicine. Full article

Post-traumatic stress disorder (PTSD) is a complex psychiatric condition characterized by persistent behavioral and neurobiological alterations following trauma. Although rodent models are commonly used to study PTSD, zebrafish (Danio rerio) have emerged as a promising alternative due to their genetic similarity to humans, conserved stress response systems, and high-throughput capabilities. This systematic review evaluates 33 experimental studies on zebrafish PTSD models, focusing on behavioral, neurochemical, and molecular outcomes. Chronic unpredictable stress (CUS/UCS) paradigms of 14–15 days were identified as the most reliable for inducing PTSD-like phenotypes, consistently resulting in anxiety-like behaviors, cortisol dysregulation, and gene expression changes. In contrast, acute stress models produced transient effects, and social defeat paradigms showed methodological variability. Chronic models frequently demonstrated neurotransmitter imbalances, oxidative stress, and upregulation of inflammatory and neuroplasticity-related genes. However, the literature revealed challenges, including protocol heterogeneity, limited sex-specific analyses, and constraints in longitudinal biomarker tracking. Future directions include epigenetic profiling, environmental standardization, and cross-species validation. When used with methodological rigor, zebrafish offer a powerful and translationally relevant platform to study PTSD mechanisms and screen novel interventions. Full article

Post-Traumatic Stress Disorder (PTSD) is a multifaceted psychiatric disorder triggered by traumatic events, leading to prolonged psychological distress and varied symptoms. Rat models have been extensively used to explore the biological, behavioral, and neurochemical underpinnings of PTSD. This review critically examines the strengths and limitations of commonly used rat models, such as single prolonged stress (SPS), stress–re-stress (S-R), and predator-based paradigms, in replicating human PTSD pathology. While these models provide valuable insights into neuroendocrine responses, genetic predispositions, and potential therapeutic targets, they face challenges in capturing the full complexity of PTSD, particularly in terms of ethological relevance and translational validity. We assess the degree to which these models mimic the neurobiological and behavioral aspects of human PTSD, highlighting areas where they succeed and where they fall short. This review also discusses future directions in refining these models to improve their utility for translational research, aiming to bridge the gap between preclinical findings and clinical applications. Full article

This retrospective study evaluated the effectiveness of different types of general anesthesia (GA) and sedation in pediatric dental procedures, focusing on treatment outcomes and follow-up compliance with an emphasis on gender differences. Clinical records of 1582 pediatric patients, aged 0–18 years, were analyzed to examine the distribution, duration and impact of anesthesia types on dental procedure complexity. The study population was divided into three age groups: 0–6, 7–12 and 13–18 years. We assessed follow-up attendance rates by gender and anesthesia type, calculated the decayed, missing and filled (DMF) index and evaluated the need for further treatment and reasons for retreatment. Our findings indicated that general anesthesia with inhalational agents and muscle relaxants was the most frequently used method (1260 instances), followed by nitrous oxide sedation (163 instances) and sevoflurane GA with a laryngeal mask airway (158 instances). Inhalational GA with muscle relaxants had the longest average duration (2.78 h) and the highest DMF index (7.43), reflecting its use in more severe dental conditions. Gender analysis revealed a slight male predominance in using inhalational GA with muscle relaxants (55.87% male vs. 44.13% female). Female patients demonstrated higher follow-up compliance across all periods. Overall, our results highlight the importance of tailored anesthesia and sedation plans, as well as follow-up protocols, in pediatric dentistry. This study provides valuable insights for practitioners in selecting appropriate anesthesia and sedation types and developing strategies to improve follow-up compliance and treatment success. Full article

Long COVID (LC), also referred to as Post COVID-19 Condition, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and other terms, represents a complex multisystem disease persisting after the acute phase of COVID-19. Characterized by a myriad of symptoms across different organ systems, LC presents significant diagnostic and management challenges. Central to the disorder is the role of low-grade inflammation, a non-classical inflammatory response that contributes to the chronicity and diversity of symptoms observed. This review explores the pathophysiological underpinnings of LC, emphasizing the importance of low-grade inflammation as a core component. By delineating the pathogenetic relationships and clinical manifestations of LC, this article highlights the necessity for an integrated approach that employs both personalized medicine and standardized protocols aimed at mitigating long-term consequences. The insights gained not only enhance our understanding of LC but also inform the development of therapeutic strategies that could be applicable to other chronic conditions with similar pathophysiological features. Full article

This study investigates audiogenic epilepsy in Krushinsky-Molodkina (KM) rats, questioning the efficacy of conventional EEG techniques in capturing seizures during animal restraint. Using a wireless EEG system that allows unrestricted movement, our aim was to gather ecologically valid data. Nine male KM rats, prone to audiogenic seizures, received implants of wireless EEG transmitters that target specific seizure-related brain regions. These regions included the inferior colliculus (IC), pontine reticular nucleus, oral part (PnO), ventrolateral periaqueductal gray (VLPAG), dorsal area of the secondary auditory cortex (AuD), and motor cortex (M1), facilitating seizure observation without movement constraints. Our findings indicate that targeted neural intervention via electrode implantation significantly reduced convulsive seizures in approximately half of the subjects, suggesting therapeutic potential. Furthermore, the amplitude of brain activity in the IC, PnO, and AuD upon audiogenic stimulus onset significantly influenced seizure severity and nature, highlighting these areas as pivotal for epileptic propagation. Severe cases exhibited dual waves of seizure generalization, indicative of intricate neural network interactions. Distinctive interplay between specific brain regions, disrupted during convulsive activity, suggests neural circuit reconfiguration in response to escalating seizure intensity. These discoveries challenge conventional methodologies, opening avenues for novel approaches in epilepsy research and therapeutic interventions. Full article

This study examines an unexplored aspect of SARS-CoV-2 entry into host cells, which is widely understood to occur via the viral spike (S) protein’s interaction with human ACE2-associated proteins. While vaccines and inhibitors targeting this mechanism are in use, they may not offer complete protection against reinfection. Hence, we investigate putative receptors and their cofactors. Specifically, we propose CD46, a human membrane cofactor protein, as a potential putative receptor and explore its role in cellular invasion, acting possibly as a cofactor with other viral structural proteins. Employing computational techniques, we created full-size 3D models of human CD46 and four key SARS-CoV-2 structural proteins—EP, MP, NP, and SP. We further developed 3D models of CD46 complexes interacting with these proteins. The primary aim is to pinpoint the likely interaction domains between CD46 and these structural proteins to facilitate the identification of molecules that can block these interactions, thus offering a foundation for novel pharmacological treatments for SARS-CoV-2 infection. Full article

Recent advances have greatly improved our understanding of the molecular mechanisms behind atherosclerosis pathogenesis. However, there is still a need to systematize this data from a general pathology perspective, particularly with regard to atherogenesis patterns in the context of both canonical and non-classical inflammation types. In this review, we analyze various typical phenomena and outcomes of cellular pro-inflammatory stress in atherosclerosis, as well as the role of endothelial dysfunction in local and systemic manifestations of low-grade inflammation. We also present the features of immune mechanisms in the development of productive inflammation in stable and unstable plaques, along with their similarities and differences compared to canonical inflammation. There are numerous factors that act as inducers of the inflammatory process in atherosclerosis, including vascular endothelium aging, metabolic dysfunctions, autoimmune, and in some cases, infectious damage factors. Life-critical complications of atherosclerosis, such as cardiogenic shock and severe strokes, are associated with the development of acute systemic hyperinflammation. Additionally, critical atherosclerotic ischemia of the lower extremities induces paracoagulation and the development of chronic systemic inflammation. Conversely, sepsis, other critical conditions, and severe systemic chronic diseases contribute to atherogenesis. In summary, atherosclerosis can be characterized as an independent form of inflammation, sharing similarities but also having fundamental differences from low-grade inflammation and various variants of canonical inflammation (classic vasculitis). Full article

Background: Amniotic fluid embolism (AFE) is one of the main causes of maternal mortality in developed countries. The most critical AFE variants may be considered from the perspective of systemic inflammation (SI), a general pathological process that includes high levels of systemic inflammatory response, neuroendocrine system distress, microthrombosis, and multiple organ dysfunction syndrome (MODS). This research work aimed to characterize the dynamics of super-acute SI using four clinical case studies of patients with critical AFE. Methods: In all the cases, we examined blood coagulation parameters, plasma levels of cortisol, troponin I, myoglobin, C-reactive protein, IL-6, IL-8, IL-10, and TNF-α, and calculated the integral scores. Results: All four patients revealed the characteristic signs of SI, including increased cytokine, myoglobin, and troponin I levels, changes in blood cortisol, and clinical manifestations of coagulopathy and MODS. At the same time, the cytokine plasma levels can be characterized not only as hypercytokinemia, and not even as a “cytokine storm”, but rather as a “cytokine catastrophe” (an increase of thousands and tens of thousands of times in proinflammatory cytokine levels). AFE pathogenesis involves rapid transition from the hyperergic shock phase, with its high levels of a systemic inflammatory response over to the hypoergic shock phase, characterized by the mismatch between low systemic inflammatory response values and the patient’s critical condition. In contrast to septic shock, in AFE there is a much more rapid succession of SI phases. Conclusion: AFE is one of the most compelling examples for studying the dynamics of super-acute SI. Full article

The physical environment of healthcare settings can promote both the healing process and patient feelings of well-being, as well as instill positive emotions in employees. The present study aimed to evaluate the dental work environment of a typical private and public dental clinic to identify key parameters that determine the perception of health facilities by patients and employees. The study was carried out from 1 to 20 December 2021, in two dental clinics in Ekaterinburg (Russian Federation) using ‘ASPECT’. The participants were 58 staff and 94 patients. The results showed that, compared with patients, staff reported higher views scores, nature and outdoors scores, and comfort and control scores. The common criterion that distinguishes private clinics from public ones was comfort and control. Compared with patients in state clinics, patients in private clinics reported higher privacy, company and dignity scores, comfort and control scores, interior appearance scores, and facility scores. In general, while views scores and nature parameters can be singled out as a universal absolute value for everyone in a particular environment, staff pay more attention to factors that contribute to long-term comfortable stay and performance of their duties. Full article

Taraxasterol (TAX), one of the active components in Dandelion, demonstrated strong antitumor properties in several cancers. However, the effect and underlying mechanism of TAX in non-small cell lung cancer (NSCLC) is unclear. In this study, we showed that TAX inhibited the proliferation of cells by inducing S-phase cell cycle arrest and prevented cell migration by interfering epithelial-mesenchymal transition (EMT) in Lewis lung cancer (LLC) cells and lung carcinoma SPC-A1 cells. The pharmacological network analysis predicted that induction of apoptosis might be the potential mechanism of TAX-mediated cell deaths. Further in vitro experiments showed that TAX could significantly induce cancer cell apoptosis as verified by increased pro-apoptotic molecules including Bax, caspase-9, and PARP1 downregulated anti-apoptotic protein Bcl-2; and decreased mitochondrial potential. The LLC subcutaneous tumor model demonstrated that TAX inhibited tumor growth by induction of apoptosis and inhibition of proliferation in vivo, which is consistent with the in vitro data. Importantly, TAX administration downregulated the proportion of Treg cells and upregulated CD107a+ NK cells in the tumor microenvironment in the tumor model. Together, these data reveal that TAX performs its antitumor effect by inducing apoptosis and modulating the tumor microenvironment, providing evidence that TAX could serve as a potential natural drug for lung cancer therapy. Full article

The healthy lifestyle of people around the world has changed dramatically during the COVID-19 pandemic. The personality risk factors for these processes from around the world remain understudied. This study aimed to examine the associations of the Big Five traits with a healthy lifestyle during the COVID-19 pandemic. In a cross-sectional study, data from 1215 Russian university students were analyzed. Participants completed the Big Five Inventory-10 and Short Multidimensional Inventory Lifestyle Evaluation. The results showed that personality traits predicted many dimensions of a healthy lifestyle during the COVID-19 pandemic. Diet and nutrition were positively predicted by extraversion, agreeableness, and conscientiousness, and it was negatively predicted by neuroticism. Substance abuse was positively predicted by agreeableness and conscientiousness, and it was negatively predicted by extraversion. Physical activity was positively predicted by extraversion and conscientiousness, and it was negatively predicted by neuroticism. Stress management was positively predicted by extraversion and conscientiousness, and it was negatively predicted by neuroticism. Restorative sleep was positively predicted by extraversion and conscientiousness, and it was negatively predicted by neuroticism. Social support for healthy practices was positively predicted by extraversion, agreeableness, and conscientiousness. Environmental exposures were positively predicted by extraversion, and neuroticism was positively and negatively predicted by conscientiousness. Our findings may be useful for further exploration of personality risk factors for healthy practices in challenging life circumstances. Full article