Search Results (7,954)

Human dermcidin (DCD) is synthesized as a 110-amino acid precursor (pre-dermcidin, pre-DCD) containing a 19-residue leader signal sequence, which is removed to produce a leader-less pro-domain-containing peptide termed as pro-dermcidin, pro-DCD. Pro-DCD can be secreted by human eccrine sweat glands and then cleaved into antimicrobial peptides, such as dermcidin (DCD). Emerging evidence suggests that pro-DCD has broader physiological roles beyond antimicrobial defense, potentially serving as a therapeutic agent for inflammatory diseases like sepsis. In this review, we summarize recent evidence supporting pro-DCD as a regulator of innate immunity in sepsis. Full article

Atherosclerosis is a progressive, multifactorial disease driven by the interplay of lipid dysregulation, chronic inflammation, oxidative stress, and maladaptive vascular remodeling. Despite advances in systemic lipid-lowering and anti-inflammatory therapies, residual cardiovascular risk persists, highlighting the need for more precise interventions. Targeted drug delivery represents a transformative strategy, offering the potential to modulate key pathogenic processes within atherosclerotic plaques while minimizing systemic exposure and off-target effects. Recent innovations span a diverse array of platforms, including nanoparticles, liposomes, exosomes, polymeric carriers, and metal–organic frameworks (MOFs), engineered to engage distinct pathological features such as inflamed endothelium, dysfunctional macrophages, oxidative microenvironments, and aberrant lipid metabolism. Ligand-based, biomimetic, and stimuli-responsive delivery systems further enhance spatial and temporal precision. In parallel, advances in in-silico modeling and imaging-guided approaches are accelerating the rational design of multifunctional nanotherapeutics with theranostic capabilities. Beyond targeting lipids and inflammation, emerging strategies seek to modulate immune checkpoints, restore endothelial homeostasis, and reprogram plaque-resident macrophages. This review provides an integrated overview of the mechanistic underpinnings of atherogenesis and highlights state-of-the-art targeted delivery systems under preclinical and clinical investigation. By synthesizing recent advances, we aim to elucidate how precision-guided drug delivery is reshaping the therapeutic landscape of atherosclerosis and to chart future directions toward clinical translation and personalized vascular medicine. Full article

As people with cystic fibrosis (PwCF) live longer, kidney disease is emerging as a significant comorbidity that is increasingly linked to cardiovascular complications and progression to end-stage kidney disease. In our recent review, we proposed the unifying term CF-related kidney disease (CFKD) to encompass the spectrum of kidney dysfunction observed in this population. Early detection of kidney injury is critical for improving long-term outcomes, yet remains challenging due to the limited sensitivity of conventional laboratory tests, particularly in individuals with altered muscle mass and unique CF pathophysiology. Emerging approaches, including novel blood and urinary biomarkers, urinary extracellular vesicles, and genetic risk profiling, offer promising avenues for identifying subclinical kidney damage. When integrated with machine learning algorithms, these tools may enable the development of personalized risk stratification models and targeted therapeutic strategies. This precision medicine approach has the potential to transform kidney disease management in PwCF, shifting care from reactive treatment of late-stage disease to proactive monitoring and early intervention. Full article

Inflammatory Bowel Diseases (IBDs) are complex, multifactorial disorders with no known cure, necessitating lifelong care and often leading to surgical interventions. This ongoing healthcare requirement, coupled with the increased use of biological drugs and rising disease prevalence, significantly increases the financial burden on the healthcare systems. Thus, a number of novel technological approaches have emerged in order to face some of the pivotal questions still associated with IBD. In navigating the intricate landscape of IBD, biosensors act as indispensable allies, bridging the gap between traditional diagnostic methods and the evolving demands of precision medicine. Continuous progress in biosensor technology holds the key to transformative breakthroughs in IBD management, offering more effective and patient-centric healthcare solutions considering the One Health Approach. Here, we will delve into the landscape of biomarkers utilized in the diagnosis, monitoring, and management of IBD. From well-established serological and fecal markers to emerging genetic and epigenetic markers, we will explore the role of these biomarkers in aiding clinical decision-making and predicting treatment response. Additionally, we will discuss the potential of novel biomarkers currently under investigation to further refine disease stratification and personalized therapeutic approaches in IBD. By elucidating the utility of biosensors across the spectrum of IBD care, we aim to highlight their importance as valuable tools in optimizing patient outcomes and reducing healthcare costs. Full article

Circadian rhythms are intrinsic 24 h cycles that regulate metabolic processes across multiple tissues, with skeletal muscle emerging as a central node in this temporal network. Muscle clocks govern gene expression, fuel utilisation, mitochondrial function, and insulin sensitivity, thereby maintaining systemic energy homeostasis. However, circadian misalignment, whether due to behavioural disruption, nutrient excess, or metabolic disease, impairs these rhythms and contributes to insulin resistance, and the development of obesity, and type 2 diabetes mellitus. Notably, the muscle clock remains responsive to non-photic cues, particularly exercise, which can reset and amplify circadian rhythms even in metabolically impaired states. This work synthesises multi-level evidence from rodent models, human trials, and in vitro studies to elucidate the role of skeletal muscle clocks in circadian metabolic health. It explores how exercise entrains the muscle clock via molecular pathways involving AMPK, SIRT1, and PGC-1α, and highlights the time-of-day dependency of these effects. Emerging data demonstrate that optimally timed exercise enhances glucose uptake, mitochondrial biogenesis, and circadian gene expression more effectively than time-agnostic training, especially in individuals with metabolic dysfunction. Finally, findings are integrated from multi-omic approaches that have uncovered dynamic, time-dependent molecular signatures that underpin circadian regulation and its disruption in obesity. These technologies are uncovering biomarkers and signalling nodes that may inform personalised, temporally targeted interventions. By combining mechanistic insights with translational implications, this review positions skeletal muscle clocks as both regulators and therapeutic targets in metabolic disease. It offers a conceptual framework for chrono-exercise strategies and highlights the promise of multi-omics in developing precision chrono-medicine approaches aimed at restoring circadian alignment and improving metabolic health outcomes. Full article

Objectives: In view of a lack of evidence on the subject, we aimed to perform a scoping review to understand the impact of health education among people attending mass gatherings. Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Guidelines. PubMed, EMBASE, Scopus, and Cochrane Library were searched from inception to March 2025 to identify eligible studies. Observational and interventional studies that reported the impact of health education on any health-related outcome among those attending a mass gathering were considered. A narrative synthesis of review results was performed to gather evidence. Recommendations were framed in the context of this evidence. Results: Of the 1731 records, only 17 studies met the inclusion criteria. These included cross-sectional (n = 10), pre-post design (n = 3), quasi-experimental (n = 2), randomized controlled trial (n = 1), and ethnographic (n = 1) studies. These studies involved participants attending hajj, umrah, and basketball events. The current evidence on health education in mass gatherings is highly varied in its objectives, intervention strategy, educational plan, mode of delivery, design, and reported outcomes. Most studies agreed that health education should be initiated by the country of origin and continued throughout the event. It is recommended that this education should be tailored to patient needs based on age, medical condition, and other personal factors, and given in the local language for better acceptability. Such sources can be provided in various forms, either online or offline, as per the participant’s convenience. Conclusions: The current evidence on the effectiveness of health education during mass gatherings, particularly in pilgrimage settings, is varied and inconsistent. Participant-tailored health education should be provided, preferably in the local language, through convenient formats. Full article

Hodgkin’s Lymphoma (HL) affects approximately 8500 individuals annually in the United States. The 5-year relative survival rate has improved to 88.5%, driven by transformative advances in immunotherapy and precision oncology. The integration of Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) has redefined treatment paradigms. The phase III SWOG S1826 trial established nivolumab plus doxorubicin, vinblastine, and dacarbazine (N + AVD) as an emerging new standard for advanced-stage HL, achieving a 2-year progression-free survival (PFS) of 92% compared to 83% for BV plus AVD (HR 0.48, 95% CI: 0.33–0.70), with superior safety, particularly in patients over 60. In relapsed/refractory HL, pembrolizumab outperforms BV, with a median PFS of 13.2 versus 8.3 months (HR 0.65, 95% CI: 0.48–0.88), as demonstrated in the KEYNOTE-204 trial. Emerging strategies, including novel ICI combinations, minimal residual disease (MRD) monitoring via circulating tumor DNA (ctDNA), and artificial intelligence (AI)-driven diagnostics, promise to further personalize therapy. This review synthesizes HL’s epidemiology, pathogenesis, diagnostic innovations, and therapeutic advances, highlighting the role of precision medicine in addressing unmet needs and disparities in HL care. Full article

Introduction: A validated clinical decision tool predictive of favorable functional outcomes following endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) remains elusive. We performed a retrospective case series of patients at our regional Comprehensive Stroke Center, over a four-year period, who have undergone EVT to elucidate patient characteristics and factors associated with a favorable functional outcome after EVT. Methods: We reviewed all cases of EVT at our institution between February 2018 and February 2022 in the extended time window from 6–24 h. Demographic, clinical, imaging, and procedure co-variates were included. A favorable clinical outcome was defined as a modified Rankin scale of 0–2. We included patients with M1 or internal carotid artery occlusion treated with EVT within 6–24 h after symptom onset. We used a univariate and multivariate logistic regression analysis to identify patient factors associated with a favorable clinical outcome at 90 days. Results: Our study included evaluation of 121 patients who underwent EVT at our comprehensive stroke center. Our analysis demonstrates that a higher recanalization score based on the modified Thrombolysis In Cerebral Infarction (mTICI) scale (2B-3) was a strong indicator of a favorable outcome (OR 7.33; CI 2.06–26.07; p = 0.0021). Our data also showed that a higher baseline National Institutes of Health Stroke Scale (NIHSS) score (p = 0.0095) and the presence of pre-existing hypertension (p = 0.0035) may also be predictors of an unfavorable outcome (mRS > 2) per our multivariate analysis. Conclusion: Patients without pre-existing hypertension had more favorable outcomes following EVT in the expanded time window. This is consistent with other multicenter data in the expanded time window that demonstrates greater odds of a poor outcome with elevated pre-, peri-, and post-endovascular-treatment blood pressure. Our data also demonstrate that the mTICI score is a strong predictor of favorable outcome, even after controlling for other variables. A lower baseline NIHSS at the time of thrombectomy may also indicate a favorable outcome. Furthermore, the presence of clinical or radiographic mismatch based on the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) and NIHSS per DAWN and DEFUSE-3 criteria did not emerge as a predictor of favorable outcome, which is congruent with recent randomized controlled trials and meta-analyses. Full article

Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article

Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS) characterized by inflammation, demyelination, axonal degeneration, and gliosis. Its pathophysiology involves a complex interplay of genetic susceptibility, environmental triggers, and immune dysregulation, ultimately leading to progressive neurodegeneration and functional decline. Although significant advances have been made in disease-modifying therapies (DMTs), many patients continue to experience disease progression and unmet therapeutic needs. Drug repurposing—the identification of new indications for existing drugs—has emerged as a promising strategy in MS research, offering a cost-effective and time-efficient alternative to traditional drug development. Several compounds originally developed for other diseases, including immunomodulatory, anti-inflammatory, and neuroprotective agents, are currently under investigation for their efficacy in MS. Repurposed agents, such as selective sphingosine-1-phosphate (S1P) receptor modulators, kinase inhibitors, and metabolic regulators, have demonstrated potential in promoting neuroprotection, modulating immune responses, and supporting remyelination in both preclinical and clinical settings. Simultaneously, artificial intelligence (AI) is transforming drug discovery and precision medicine in MS. Machine learning and deep learning models are being employed to analyze high-dimensional biomedical data, predict drug–target interactions, streamline drug repurposing workflows, and enhance therapeutic candidate selection. By integrating multiomics and neuroimaging data, AI tools facilitate the identification of novel targets and support patient stratification for individualized treatment. This review highlights recent advances in drug repurposing and discovery for MS, with a particular emphasis on the emerging role of AI in accelerating therapeutic innovation and optimizing treatment strategies. Full article

The relationship between metabolic dysfunction and mental health disorders is complex and has received increasing attention. This review integrates current research to explore how stress-related growth differentiation factor 15 (GDF15) signaling, ceramides derived from gut microbiota, and mitochondrial dysfunction in the brain interact to influence both metabolic and psychiatric conditions. Evidence suggests that these pathways converge to regulate brain energy homeostasis through feedback mechanisms involving the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. GDF15 emerges as a key stress-responsive biomarker that links peripheral metabolism with brainstem GDNF family receptor alpha-like (GFRAL)-mediated anxiety circuits. Meanwhile, ceramides impair hippocampal mitochondrial function via membrane incorporation and disruption of the respiratory chain. These disruptions may contribute to sustained pathological states such as depression, anxiety, and cognitive dysfunction. Although direct mechanistic data are limited, integrating these pathways provides a conceptual framework for understanding metabolic–psychiatric comorbidities. Furthermore, differences in age, sex, and genetics may influence these systems, highlighting the need for personalized interventions. Targeting mitochondrial function, GDF15-GFRAL signaling, and gut microbiota composition may offer new therapeutic strategies. This integrative perspective helps conceptualize how metabolic and psychiatric mechanisms interact for understanding the pathophysiology of metabolic and psychiatric comorbidities and highlights therapeutic targets for precision medicine. Full article

Recent studies have demonstrated that the development and progression of hypertensive kidney injury comprise not only elevated systemic blood pressure but also a complex interplay of cellular, molecular, and genetic mechanisms. In this report, we outline the key emerging pathways—ranging from dysregulated renin–angiotensin system signaling, oxidative stress, immune-mediated inflammation, and metabolic abnormalities to epigenetic alterations and genetic susceptibilities—that contribute to kidney damage in hypertensive conditions. In addition, we also discuss precision medicine approaches like biomarker-directed therapies, pharmacologically targeted therapies, and device-based innovations for modulating these pathways. This integrative review emphasizes the application of omics technologies and genetically guided interventions to better stratify patients and offer personalized care for hypertensive kidney disease. Full article

Platelet-rich plasma (PRP) is widely used in regenerative medicine, yet clinical outcomes remain inconsistent. While traditional strategies have focused on platelet concentration and activation methods, emerging evidence suggests that the biological age of platelets, especially platelet senescence, may be a critical but overlooked factor influencing therapeutic efficacy. Senescent platelets display reduced granule content, impaired responsiveness, and heightened pro-inflammatory behavior, all of which can compromise tissue repair and regeneration. This review explores the mechanisms underlying platelet aging, including oxidative stress, mitochondrial dysfunction, and systemic inflammation, and examines how these factors influence PRP performance across diverse clinical contexts. We discuss the functional consequences of platelet senescence, the impact of comorbidities and aging on PRP quality, and current tools to assess platelet functionality, such as HLA-I–based flow cytometry. In addition, we present strategies for pre-procedural optimization, advanced processing techniques, and adjunctive therapies aimed at enhancing platelet quality. Finally, we challenge the prevailing emphasis on high-volume blood collection, highlighting the limitations of quantity-focused protocols and advocating for a shift toward biologically precise, function-driven regenerative interventions. Recognizing and addressing platelet senescence is a key step toward unlocking the full therapeutic potential of PRP-based interventions. Full article

Objectives: Early death after trauma has been described several times. Little is known about it after traumatic brain injury (TBI) and decompressive craniectomy (DC). The aim of this study was to characterize patients who die after a TBI and DC during their in-hospital stay. Methods: In a subgroup analysis of a retrospective, multicenter, and observational study, non-survivors from in-hospital stays treated for severe TBI and DC were included. Propensity score matching (PSM) was used. Results: A total of 223 patients with severe TBI were treated with DC, and there were 65 (29.1%) patients who did not survive. Of these, 22 (33.8%) died within the first 24 h. Non-survivors were older (p = 0.010), and pupillomotor dysfunction and a higher heart rate on admission were more common (p < 0.001). PSM patients for overall survival (41, 18.4%) differed in mean heart rate from the deceased (p = 0.030). In a multivariate model, age (OR: 1.045, p = 0.013, CI95%: 1.010 to 1.082), Quick value (OR: 0.965, p = 0.049, CI95%: 0.931 to 1.000), and heart rate (OR: 1.099, p = 0.030, CI95%: 1.009 to 1.197) were confirmed as predictive factors. Conclusions: Even after DC, known factors, such as chronological age and comorbidities, have a significant influence on mortality. The value of DC in an aging society for a particular severity of TBI should be further assessed on the basis of prospective studies. Full article

Colorectal cancer (CRC) constitutes a major global health concern, ranking as the third most common cancer and the second leading cause of cancer-related mortality. The current review explores sex-based differences in CRC epidemiology, risk factors, tumor biology, and clinical outcomes. Males exhibit a higher incidence and mortality rate, with left-sided (distal) CRC predominating, while females are more frequently diagnosed with right-sided (proximal) tumors, which tend to be more aggressive and less responsive to conventional chemotherapy. Genetic disparities, including microsatellite instability and X-chromosome tumor suppressor genes, contribute to sex-specific differences in tumor progression and treatment response. Immune variations also influence disease outcomes, with females exhibiting stronger immune surveillance but higher exhaustion markers. Lifestyle factors such as body mass index (BMI), smoking, and hormonal influences further modulate CRC risk. While males are more vulnerable to obesity-related CRC, central obesity (waist-to-hip ratio) emerges as a stronger predictor in females. Additionally, smoking increases CRC risk differentially by tumor location. These findings underscore the importance of sex-specific approaches in CRC prevention, screening, and treatment, advocating for personalized medicine strategies tailored to gender-based biological and clinical distinctions. Full article