Search Results (198)

Fusobacterium nucleatum (Fn) has been increasingly recognized as a crucial mediator of colorectal cancer (CRC) biology, particularly in microsatellite-stable (MSS) tumors, where immune checkpoint inhibitors (ICIs) have shown limited efficacy. Rather than representing a passive microbial passenger, Fn actively shapes tumor behavior by adhering to epithelial cells, activating oncogenic signaling, and promoting epithelial–mesenchymal transition (EMT). At the same time, it remodels the tumor microenvironment, driving immune suppression through inhibitory receptor engagement, accumulation of myeloid-derived cells, and metabolic reprogramming of tumor-associated macrophages. These mechanisms converge to impair cytotoxic immunity and contribute to both intrinsic and acquired resistance to ICIs. Beyond immune escape, Fn interferes with conventional chemotherapy by sustaining autophagy and blocking ferroptosis, thereby linking microbial colonization to multidrug resistance. Most of these mechanisms derive from preclinical in vitro and in vivo models, where causal relationships can be inferred. In contrast, human data are mainly observational and provide correlative evidence without proving causality. No interventional clinical studies directly targeting Fn have yet been conducted. Its enrichment across the adenoma–carcinoma sequence and consistent detection in both tumor and fecal samples highlight its potential as a biomarker for early detection and patient stratification. Importantly, multidimensional stool assays that integrate microbial, genetic, and epigenetic markers are emerging as promising non-invasive tools for CRC screening. Therapeutic strategies targeting Fn are also under exploration, ranging from antibiotics and bacteriophages to multifunctional nanodrugs, dietary modulation, and natural microbiota-derived products. These approaches may not only reduce microbial burden but also restore immune competence and enhance the efficacy of immunotherapy in MSS CRC. Altogether, current evidence positions Fn at the intersection of microbial dysbiosis, tumor progression, and therapy resistance. A deeper understanding of its pathogenic role may support the integration of microbial profiling into precision oncology frameworks, paving the way for innovative diagnostic and therapeutic strategies in CRC. Full article

Background: Intervertebral disc degeneration (IVDD) is closely linked to low back pain (LBP), a leading cause of disability worldwide. IVDD is characterized by the loss of proteoglycans (PGs), extracellular matrix (ECM) degradation, and reduced hydration of the nucleus pulposus (NP). Extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) exhibit tissue repair and immunomodulatory effects and are emerging as promising cell-free therapeutics. Methods: We established a rat IVDD model via fluoroscopy-guided needle puncture of three consecutive coccygeal discs and confirmed degeneration through Alcian Blue and hematoxylin & eosin (H&E) staining. The gene expression of inflammatory and pain markers (ADRβ2, COMP, CXCL1, COX2, PPTA, MMP13, YKL40) was measured by qPCR. Subsequently, we implanted hUC-MSCs or EVs to evaluate their reparative potential. Results: Upregulation of inflammatory and pain genes in IVDD was associated with an immunomodulatory response. Tracking DiI-labelled hUC-MSCs and EVs revealed enhanced survival of hUC-MSCs, retention of EVs, and dispersion within rat tail discs; EVs showed greater retention than hUC-MSCs. Implanted EVs were internalized by NP cells and remained within degenerative IVDs. EVs passively diffused, accumulated at the injury site, interacted with host cells, and enhanced function, as shown by increased expression of human chondrocyte-related markers (SOX9, TGFβ1, TGFβ2, COL2) compared to hUC-MSC treatment. Histological analysis of two weeks post-transplantation showed NP cellular patterns resembling chondromas in treated discs. EVs integrated into and distributed within degenerated NP regions, with greater glycosaminoglycan (GAG) content. Conclusions: Overall, hUC-MSC EVs demonstrated superior regenerative capacity, supporting a safe, cell-free strategy for disc repair. Full article

Brucellosis remains an underreported zoonotic disease in Ecuador. Its control program in cattle integrates diagnostic testing, vaccination, and eradication incentives, although participation is largely voluntary. Since 2025, vaccination has become compulsory nationwide. Human surveillance remains largely passive, and strain-level data are very limited. This study applied an integrated approach, combining serology (Rose Bengal and SAT-EDTA), microbiological culture, and molecular diagnostics, to assess the presence and diversity of Brucella spp. in cattle and pigs from six slaughterhouses in the northern Andean highlands. A total of 2054 cattle and 1050 pigs from Carchi, Imbabura, and Pichincha were sampled. Among cattle, 133 (6.5%; 95% CI: 5.5–7.6) were seropositive, and viable B. abortus strains were isolated from 17 (12.8%). Genus identification was confirmed by IS711-PCR, while species- and biovar-level differentiation was achieved with AMOS-PCR; additional assays targeting the ery gene and RB51 marker were used to distinguish field from vaccine strains. Biotyping and molecular analysis revealed a predominance of B. abortus biovar 4 (13/17 isolates) over biovar 1, all confirmed as field strains. In pigs, 10 animals (0.95%) tested seropositive, but no isolates were recovered, highlighting limitations of serology in swine. Most livestock, including the positives, originated locally, reinforcing the representativeness of our findings. The successful isolation and molecular characterization of B. abortus demonstrates the value of combining diagnostic strategies beyond serology. These results underscore the utility of active surveillance when supported by traceability systems; this approach may also contribute to guide interventions to reduce infection risk in livestock and humans. Full article

The aorta, once viewed as a passive conduit, is now recognized as an active organ crucial for hemodynamic regulation and vascular homeostasis. Thoracic aortic aneurysms (TAAs), particularly those involving the ascending aorta, often remain silent until life-threatening complications such as dissection or rupture occur. Current management primarily relies on aortic diameter criteria, yet up to 60% of type A dissections occur at sizes below the 5.5 cm surgical threshold, revealing the limitations of this approach. This narrative review summarizes recent advances in understanding ascending aortic aneurysms, including insights into their genetic and degenerative mechanisms, the role of novel morphological and hemodynamic markers, and the potential of advanced imaging techniques. It also explores evolving surgical strategies, from conventional open repair, still the gold standard, to minimally invasive and investigational endovascular approaches. By integrating biological, morphological, and clinical factors, emerging strategies aim to move beyond diameter alone toward more personalized risk assessment. This paradigm shift may improve early detection, optimize surgical timing, and ultimately enhance outcomes for patients with ascending aortic aneurysms. Full article

Acute kidney injury (AKI) is a frequent and severe complication in trauma patients, affecting up to 28% of intensive care unit (ICU) admissions and contributing significantly to morbidity, mortality, and long-term renal impairment. Trauma-related AKI (TRAKI) arises from diverse mechanisms, including hemorrhagic shock, ischemia–reperfusion injury, systemic inflammation, rhabdomyolysis, nephrotoxicity, and complex organ crosstalk involving the brain, lungs, and abdomen. Pathophysiologically, TRAKI involves early disruption of the glomerular filtration barrier, tubular epithelial injury, and renal microvascular dysfunction. Inflammatory cascades, oxidative stress, immune thrombosis, and maladaptive repair mechanisms mediate these injuries. Trauma-related rhabdomyolysis and exposure to contrast agents or nephrotoxic drugs further exacerbate renal stress, particularly in patients with pre-existing comorbidities. Traditional markers such as serum creatinine (sCr) are late indicators of kidney damage and lack specificity. Emerging structural and stress response biomarkers—such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), interleukin-18 (IL-18), C-C motif chemokine ligand 14 (CCL14), Dickkopf-3 (DKK3), and the U.S. Food and Drug Administration (FDA)-approved tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein 7 (TIMP-2 × IGFBP-7)—allow earlier detection of subclinical AKI and better predict progression and the need for renal replacement therapy. Together, functional indices like urinary sodium and fractional potassium excretion reflect early microcirculatory stress and add clinical value. In parallel, risk stratification tools, including the Renal Angina Index (RAI), the McMahon score, and the Haines model, enable the early identification of high-risk patients and help tailor nephroprotective strategies. Together, these biomarkers and risk models shift from passive AKI recognition to proactive, personalized management. A new paradigm that integrates biomarker-guided diagnostics and dynamic clinical scoring into trauma care promises to reduce AKI burden and improve renal outcomes in this critically ill population. Full article

Background/Objectives: Mental fatigue during driving, whether passive (arising from monotony) or active (caused by cognitive overload), is a critical factor for road safety. Despite the growing interest in monitoring techniques based on neurophysiological signals, current biomarkers are primarily validated only for detecting passive mental fatigue under monotonous conditions. The objective of this study is to evaluate the sensitivity of the MDrow index, which is based on EEG Alpha band activity, previously validated for detecting passive mental fatigue, with respect to active mental fatigue, i.e., the mental fatigue occurring in cognitively demanding driving scenarios. Methods: A simulated experimental protocol was developed featuring three driving scenarios with increasing complexity: monotonous, urban, and urban with dual tasks. Nineteen participants took part in the experiment, during which electroencephalogram (EEG), photoplethysmogram (PPG), and electrodermal activity (EDA) data were collected in addition to subjective assessments, namely the Karolinska Sleepiness Scale (KSS) and the Driving Activity Load Index (DALI) questionnaires. Results:The findings indicate that MDrow shows sensitivity to both passive and active mental fatigue (p < 0.001), thereby demonstrating stability even in the presence of additional cognitive demands. Furthermore, Heart Rate (HR) and Heart Rate Variability (HRV) increased significantly during the execution of more complex tasks, thereby suggesting a heightened response to mental workload in comparison to mental fatigue alone. Conversely, electrodermal measures evidenced no sensitivity to mental fatigue-related changes. Conclusions: These findings confirm the MDrow index’s validity as an objective and continuous marker of mental fatigue, even under cognitively demanding conditions. Full article

CD44, a multi-isoform adhesion receptor for hyaluronic acid (HA), plays a crucial role in regulating cell interactions with the extracellular matrix, cell migration, differentiation, and survival in both physiological and pathological contexts. Accumulating experimental evidence suggests that CD44 is not merely a passive marker of mesenchymal cell activation but rather an active signaling hub driving fibrosis in many organs, including the lung, skin, heart, and liver. Its involvement in fibroblast differentiation into myofibroblasts, as well as induction of the invasive phenotype of these cells, shows striking analogies to the mechanisms of epithelial-to-mesenchymal transition (EMT) known from cancer progression. In this paper, we discuss both the molecular mechanisms of CD44-dependent signaling (including through EGFR, MAPK/ERK, CaMKII, lipid rafts, and Smad) and the influence of its modulation (knockout, antibodies, blockade of HA synthesis) on the course of fibrosis in in vitro and in vivo models. In addition, we present the influence of environmental pollutants—such as heavy metals, particulate matter, endocrine disruptors, and microplastics—on the activation of the HA-CD44 axis in connective tissue, with particular emphasis on their role in the induction of chronic inflammation, EMT, and extracellular matrix deposition. The collected evidence suggests that CD44 serves as a central integrator of inflammatory and fibrogenic signals, and its pharmacological modulation may represent a novel therapeutic strategy for treating fibrotic diseases and chronic inflammatory conditions. Full article

Background: This study examined the effects of repeated ischemic preconditioning (IPC) combined with normobaric hypoxia on anaerobic performance and physiological stress markers. Methods: Fourteen physically active males (22.3 ± 3.1 years) completed three randomized, single-blind crossover sessions under the following conditions: (1) normoxia (NOR), (2) normobaric hypoxia (HYP; FiO₂ = 14.7%), and (3) hypoxia with IPC (IPC-HYP). Each session included three 30 s cycling Wingate tests separated by four minutes of passive recovery. Blood samples were collected pre-exercise, immediately post-exercise, and 15 min post-exercise to assess lactate, pH, bicarbonate (HCO₃⁻), and creatine kinase (CK) activity. Results: Peak power output was highest under NOR during Wingate II and III. IPC-HYP attenuated the decline in peak power compared to that under HYP (e.g., Wingate II: 15.56 vs. 12.52 W/kg). IPC-HYP induced greater lactate accumulation (peak: 15.45 mmol/L, p < 0.01), more pronounced acidosis (pH: 7.18 post-exercise), and lower bicarbonate (9.9 mmol/L, p < 0.01). CK activity, measured immediately and then 1 h and 24 h post-exercise, was highest under IPC-HYP at 24 h (568.5 U/L). Conclusions: IPC-HYP mitigates the decline in peak anaerobic power observed under hypoxia, despite eliciting greater metabolic and muscular stress. These findings suggest that IPC may enhance physiological adaptation to hypoxic training, potentially improving anaerobic performance. Full article

Chronic kidney disease of unknown origin (CKDu) is a public health concern, particularly in agricultural communities, with multiple environmental exposures hypothesized as potential contributors. This study employed a targeted exposure assessment using personal silicone wristbands to characterize chemical exposures among women living and working in CKDu-affected regions of Guatemala. Participants wore wristbands for seven days, passively sampling air and dermal exposures. Overall, 45 wristbands were collected from 37 female participants (19 sugarcane workers and 18 community members). Of the 1530 chemicals measured using a single semi-quantitative method, 103 were detected, with an average of 27 chemicals per wristband (range: 16–40). Polycyclic aromatic hydrocarbon (PAH) levels were higher in community members’ wristbands, whereas workers exhibited higher exposure to pesticides (i.e., pendimethalin and fipronil). Workers had worse kidney function compared to community members, with almost half of the workers having an estimated glomerular filtration rate, eGFR, <90 mL/min/1.73 m². Correlations were observed between kidney function markers and specific chemicals, with the strongest correlation between albumin-to-creatinine ratio and pyrene levels (ρ = 0.57, p < 0.01) among workers. Women in agricultural regions of Guatemala experience widespread exposure to diverse environmental chemicals, some of which may contribute to kidney function decline. Full article

This study focuses on the issue of whether orally administered zinc (gluconate) (26 mg BID) can induce the remodeling of gastrointestinal barrier function and reduce passive leak across the human intestinal mucosal barrier in situ. Increased transmucosal leak has been implicated in diseases as diverse and seemingly unconnected as Inflammatory Bowel Disease (IBD), Celiac Disease, Autism Spectrum Disorders and Alzheimer’s Dementia. Our current investigation represents the first patient-based study to examine the effect of zinc on gastrointestinal epithelial tight junctions and gastrointestinal barrier leak in otherwise healthy test subjects. Using independent test subject groups for each endpoint, three separate molecular analyses indicated that zinc treatment can achieve a positive outcome: (1) RNA-seq analyses of intestinal biopsies showed salutary patterns of gene transcription changes dealing with not only transcripts of junctional proteins but also transcripts mitigating the proinflammatory state, as well as dedifferentiation (both modulators of tight junction permeability); (2) Western immunoblot analyses of intestinal tissue indicated that tight junctional protein expression was being modified by the administered zinc, most notably Claudin-2 and Tricellulin; (3) zinc treatment induced a reduction in serum levels of a functional marker of passive intestinal leak, namely the GI microbiome metabolite D-Lactate. The data collectively suggest that orally administered zinc can induce remodeling of the intestinal epithelial barrier, resulting in the reduction in GI barrier leak. The overall safety and economy of supplement levels of zinc suggest that this micronutrient could be efficacious as an adjuvant therapy to reduce the condition known as leaky gut, and possibly therefore be protective regarding diseases postulated to involve leaky gut. Full article

A comprehensive UPLC-MS/MS method was developed and validated for the simultaneous separation and quantification of atenolol, propranolol, quinidine, and verapamil, using established intestinal permeability standards in the Caco-2 cell monolayer model. This in vitro model is widely accepted for predicting intestinal drug permeability and is formally recognized by global regulatory agencies, including the FDA, EMA, and WHO, as a surrogate for assessing drug permeability in biowaiver applications under the Biopharmaceutics Classification System (BCS) framework. Despite its regulatory importance, standardized methods for the simultaneous quantification of key permeability markers remain scarce. The selected compounds represent distinct transport pathways: paracellular (atenolol), passive transcellular (propranolol, verapamil), and P-glycoprotein-mediated efflux (quinidine). Method validation followed FDA guidelines and demonstrated high selectivity, linearity (r² > 0.998), precision, and accuracy. Solid-phase extraction enhanced recovery and reduced matrix effects. Application to Caco-2 permeability assays confirmed expected transport profiles, including P-gp inhibition effects with verapamil. By integrating multiple analytes in a single workflow, the method improves analytical throughput, supports mechanistic interpretation, and ensures consistency across assays. This advanced separation strategy, combined with sensitive mass spectrometric detection, supports regulatory and BCS-based classification studies, contributing to the standardization of permeability assessments in drug development. Full article

Contemporary visual assistive devices often lack immersive user experience due to passive control systems. This study introduces a neuronally controlled visual assistive device (NCVAD) that aims to assist visually impaired users in performing reach tasks with active, intuitive control. The developed NCVAD integrates computer vision, electroencephalogram (EEG) signal processing, and robotic manipulation to facilitate object detection, selection, and assistive guidance. The monocular vision-based subsystem implements the YOLOv8n algorithm to detect objects of daily use. Then, audio prompting conveys the detected objects’ information to the user, who selects their targeted object using a voluntary trigger decoded through real-time EEG classification. The target’s physical coordinates are extracted using ArUco markers, and a gradient descent-based path optimization algorithm (POA) guides a 3-DoF robotic arm to reach the target. The classification algorithm achieves over 85% precision and recall in decoding EEG data, even with coexisting physiological artifacts. Similarly, the POA achieves approximately 650 ms of actuation time with a 0.001 learning rate and 0.1 cm² error threshold settings. In conclusion, the study also validates the preliminary analysis results on a working physical model and benchmarks the robotic arm’s performance against human users, establishing the proof-of-concept for future assistive technologies integrating EEG and computer vision paradigms. Full article

Endogenous retroviruses (ERVs) are remnants of retroviral infections that have become stably integrated into host germline genomes. Far beyond passive genomic elements, ERVs actively shape host evolution through complex mechanisms involving genetic innovation, immune modulation, and species adaptation. This review provides a comprehensive synthesis of ERV biology, highlighting recent advances in their classification, amplification mechanisms, and epigenetic silencing. Particular emphasis is placed on the cross-talk between ERVs and exogenous retroviruses (XRVs), demonstrating how receptor competition, recombination, and immune evasion contribute to virus-host co-evolution. We explore ERVs as molecular markers for phylogenetic reconstruction, with case studies such as Koala retrovirus (KoRV) and HERV-K illustrating regional transmission dynamics and co-opted immune functions. Additionally, we discuss the functional domestication of ERVs into regulatory elements, non-coding RNAs, and envelope-derived fusion proteins that influence gene expression, antiviral defense, and placental development. Full article

Bone integrity is maintained through continuous remodeling, orchestrated by the coordinated actions of osteocytes, osteoblasts, and osteoclasts. Once considered passive bystanders, osteocytes are now recognized as central regulators of this process, mediating biochemical signaling and mechanotransduction. Malfunctioning osteocytes contribute to serious skeletal disorders such as osteoporosis. Mesenchymal stromal cells (MSCs), multipotent stem cells capable of differentiating into osteoblasts, have emerged as promising agents for bone regeneration, primarily through the paracrine effects of their secreted exosomes. MSC-derived exosomes are nanoscale vesicles enriched with proteins, lipids, and nucleic acids that promote intercellular communication, osteoblast proliferation and differentiation, and angiogenesis. Notably, they deliver osteoinductive microRNAs (miRNAs) that influence osteogenic markers and support bone tissue repair. In vivo investigations validate their capacity to enhance bone regeneration, increase bone volume, and improve biomechanical strength. Additionally, MSC-derived exosomes regulate the immune response, creating pro-osteogenic and pro-angiogenic factors, boosting their therapeutic efficacy. Due to their cell-free characteristics, MSC-derived exosomes offer benefits such as diminished immunogenicity and minimal risk of off-target effects. These properties position them as promising and innovative approaches for bone regeneration, integrating immunomodulatory effects with tissue-specific regenerative capabilities. Full article

Traditional 2D optical markers degrade quickly in underwater applications due to sediment accumulation and marine biofouling, becoming undetectable within weeks. This paper presents a Three-Dimensional Binary Marker, a novel passive fiducial marker designed for underwater Long-Term Deployment. The Three-Dimensional Binary Marker addresses the 2D-markers limitation through a 3D design that enhances resilience and maintains contrast for computer vision detection over extended periods. The proposed solution has been validated through simulation, water tank testing, and long-term sea trials for 5 months. In each stage, the marker was compared based on detection per visible frame and the detection distance. In conclusion, the design demonstrated superior performance compared to standard 2D markers. The proposed Three-Dimensional Binary Marker provides compatibility with widely used fiducial markers, such as ArUco and AprilTag, allowing quick adaptation for users. In terms of fabrication, the Three-Dimensional Binary Marker uses additive manufacturing, offering a low-cost and scalable solution for underwater localization tasks. The proposed marker improved the deployment time of fiducial markers from a couple of days to sixty days and with a range up to seven meters, providing robustness and reliability. As the marker survivability and detection range depend on its size, it is still a valuable innovation for Autonomous Underwater Vehicles, as well as for inspection, maintenance, and monitoring tasks in marine robotics and offshore infrastructure applications. Full article