Search Results (6,037)

Gut dysbiosis and an inflamed bowel are growing concerns in mammals, including dogs. Probiotic supplements have been used to restore the natural microbial community and improve gastrointestinal health. Biofilm formation, antimicrobial activities, and immunological responses of probiotics are crucial to improving gut health. Thus, we tested a commercial probiotic blend (LabMAX-3), a canine kibble additive comprising Lactobacillus acidophilus, Lacticaseibacillus casei, and Enterococcus faecium for their ability to inactivate common enteric pathogens; their ability to form biofilms; epithelial cell adhesion; and their anti-inflammatory response in the Madin-Darby Canine Kidney (MDCK) cell line. Probiotic LabMAX-3 blend or individual isolates showed a strong inhibitory effect against Salmonella enterica, Listeria monocytogenes, enterotoxigenic Escherichia coli, and Campylobacter jejuni. LabMAX-3 formed biofilms comparable to Staphylococcus aureus. LabMAX-3 adhesion to the MDCK cell line (with or without lipopolysaccharide (LPS) pretreatment) showed comparable adhesion and biofilm formation (p < 0.05) to L. casei ATCC 334 used as a control. LabMAX-3 had no cytotoxic effects on the MDCK cell line during 1 h exposure. The interleukin-10 (IL-10) and tumor necrosis factor alpha (TNFα) ratio of LabMAX-3, compared to the L. casei control, showed a significant increase (p < 0.05), indicating a more pronounced anti-inflammatory response. The data show that LabMAX-3, a canine kibble supplement, can improve gastrointestinal health. Full article

The Notch signaling pathway plays a major role in embryological development and in the ongoing life processes of many animals. Its role is to provide cell-to-cell communication in which a Sender cell, bearing membrane-embedded ligands, instructs a Receiver cell, bearing membrane-embedded receptors, to adopt one of two available fates. Elucidating the evolution of this pathway is the topic of this paper, which uses an orthologs approach, providing a comprehensive basis for the study. Using BLAST searches, orthologs were identified for all the 49 components of the Notch signaling pathway. The historical time course of integration of these proteins, as the animals evolved, was elucidated. Insofar as cell-to-cell communication is of relevance only in multicellular animals, it is not surprising that the Notch system became functional only with the evolutionary appearance of Metazoa, the first multicellular animals. Porifera contributed a quarter of the Notch pathway proteins, the Cnidaria brought the total to one-half, but the system reached completion only when humans appeared. A literature search elucidated the roles of the Notch system’s components in modern descendants of the ortholog-contributing ancestors. A single protein, the protein tyrosine kinase (PTK) of the protozoan Ministeria vibrans, was identified as a possible pre-Metazoan ancestor of all three of the Notch pathway proteins, DLL, JAG, and NOTCH. A scenario for the evolution of the Notch signaling pathway is presented and described as the co-option of its components, clade by clade, in a repurposing of genes already present in ancestral unicellular organisms. Full article

Background/Objectives: The development of therapies targeting unregulated Src signaling through selective kinase inhibition using small-molecule inhibitors presents a significant challenge for the scientific community. Among these inhibitors, pyrazolo[3,4-d]pyrimidine heterocycles have emerged as potent agents; however, their clinical application is hindered by low solubility in water. To overcome this limitation, some carrier systems, such as halloysite nanotubes (HNTs), can be used. Methods: Herein, we report the development of HNT-based nanomaterials as carriers for pyrazolo[3,4-d]pyrimidine molecules. To achieve this objective, the clay was modified by two different approaches: supramolecular loading into the HNT lumen and covalent grafting onto the HNT external surface. The resulting nanomaterials were extensively characterized, and their morphology was imaged by high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM). In addition, the kinetic release of the molecules supramolecularly loaded into the HNTs was also evaluated. QSAR studies were conducted to elucidate the physicochemical and pharmacokinetic properties of these inhibitors, and structure-based virtual screening (SBVS) was performed to analyze their binding poses in protein kinases implicated in cancer. Results: The characterization methods demonstrate successful encapsulation of the drugs and the release properties under physiological conditions. Furthermore, QSAR studies and SBVS provide valuable insights into the physicochemical, pharmacokinetic, and binding properties of these inhibitors, reinforcing their potential efficacy. Conclusions: The cytotoxicity of these halloysite-based nanomaterials, and of pure molecules for comparison, was tested on RT112, UMUC3, and PC3 cancer cell lines, demonstrating their potential as effective agents for prostate and bladder cancer treatment. Full article

Planktonic unicellular cyanobacteria are the dominant biomass producers and carbon fixers in the global ocean ecosystem, but they are not abundant in polar seawater. The interseasonal dynamics of picocyanobacterial (PC) abundance, picophytoplankton primary production, and phylogenetic diversity of PC Synechococcus were studied in the sub-Arctic White Sea. The PC abundance varied from 0.2–0.3 × 10⁶ cells/L in February to 5.2–16.7 × 10⁶ cells/L in July. Picophytoplankton primary production ranged from 0.22 mg C/m³ per day in winter to 11.32 mg C/m³ per day in summer. Synechococcus abundance positively correlated with water temperature and river discharge that increased in recent years in the White Sea. Phylogenetic analysis of the 16S rRNA gene and ITS region clone libraries from the White Sea and Barents Sea eDNA revealed picocyanobacterial sequences related to marine Synechococcus subclusters 5.1-I, 5.I-IV, 5.2, and 5.3. All Synechococcus S5.1-I were common in the White and Barents seas and were consistently present in the picophytoplankton composition throughout the year. Synechococcus S5.2 and S5.3 appear in the PC community in summer, suggesting their river origin, and Synechococcus S5.1-IV inhabits only the Barents Sea and was not detected in the White Sea. A unique Synechococcus phylotype was revealed. It is expected that the increase in the abundance of PC and their increasing role in ecosystem functioning, as well as the enrichment of the species composition with new phylotypes in the semi-enclosed sub-Arctic White Sea, which is vulnerable to the effects of climate change, will be characteristic of all Arctic seas in general. Full article

In recent years, the application of machine learning methods has become increasingly common in atmospheric science, particularly in modeling and predicting processes that impact air quality. This study focuses on predicting hydrogen production from solid oxide electrolytic cells (SOECs), a technology with significant potential for reducing greenhouse gas emissions and improving air quality. We developed two models using artificial neural networks (ANNs) and support vector machine (SVM) to predict hydrogen production. The input variables are current, voltage, communication delay time, and real-time measured hydrogen production, while the output variable is hydrogen production at the next sampling time. Both models address the critical issue of production hysteresis. Using 50 h of SOEC system data, we evaluated the effectiveness of the ANN and SVM methods, incorporating hydrogen production time as an input variable. The results show that the ANN model is superior to the SVM model in terms of hydrogen production prediction performance. Specifically, the ANN model shows strong predictive performance at a communication delay time ε = 0.01–0.02 h, with RMSE = 2.59 × 10⁻², MAPE = 33.34 × 10⁻²%, MAE = 1.70 × 10⁻² Nm³/h, and R² = 99.76 × 10⁻². At delay time ε = 0.03 h, the ANN model yields RMSE = 2.74 × 10⁻² Nm³/h, MAPE = 34.43 × 10⁻²%, MAE = 1.73 × 10⁻² Nm³/h, and R² = 99.73 × 10⁻². Using the SVM model, the prediction error values at delay time ε = 0.01–0.02 h are RMSE = 2.70 × 10⁻² Nm³/h, MAPE = 44.01 × 10⁻²%, MAE = 2.24 × 10⁻² Nm³/h, and R² = 99.74 × 10⁻², while at delay time ε = 0.03 h they become RMSE = 2.67 × 10⁻² Nm³/h, MAPE = 43.44 × 10⁻²%, MAE = 2.11 × 10⁻² Nm³/h, and R² = 99.75 × 10⁻². With this precision, the ANN model for SOEC hydrogen production prediction has positive implications for air pollution control strategies and the development of cleaner energy technologies, contributing to overall improvements in air quality and the reduction of atmospheric pollutants. Full article

Competition between bacterial species is a major factor shaping microbial communities. It is possible but remains largely unexplored that competition between bacterial pathogens can be mediated through antagonistic effects of bacterial effector proteins on host systems, particularly the actin cytoskeleton. Using Salmonella Typhimurium invasion into cells as a model, we demonstrate that invasion is inhibited if the host actin cytoskeleton is disturbed by actin-specific toxins, namely, Vibrio cholerae MARTX actin crosslinking (ACD) and Rho GTPase inactivation (RID) domains, Photorhabdus luminescens TccC3, and Salmonella’s own SpvB. We noticed that ACD, being an effective inhibitor of tandem G-actin-binding assembly factors, is likely to inhibit the activity of another Vibrio effector, VopF. In reconstituted actin polymerization assays and by live-cell microscopy, we confirmed that ACD potently halted the actin nucleation and pointed-end elongation activities of VopF, revealing competition between these two V. cholerae effectors. These results suggest that bacterial effectors from different species that target the same host machinery or proteins may represent an effective but largely overlooked mechanism of indirect bacterial competition in host-associated microbial communities. Whether the proposed inhibition mechanism involves the actin cytoskeleton or other host cell compartments, such inhibition deserves investigation and may contribute to a documented scarcity of human enteric co-infections by different pathogenic bacteria. Full article

Drug discovery is associated with high levels of compound elimination in all stages of development. The current practices for the pharmacokinetic testing of intestinal absorption combine Transwell^® inserts with the Caco-2 cell line and are associated with a wide range of limitations. The improvement of pharmacokinetic research relies on the development of more advanced in vitro intestinal constructs that better represent human native tissue and its response to drugs, providing greater predictive accuracy. Here, we present a humanized, bioengineered intestinal construct that recapitulates aspects of intestinal microanatomy. We present improved histotypic characteristics reminiscent of the human intestine, such as a reduction in transepithelial electrical resistance (TEER) and the formation of a robust basement membrane, which are contributed to in-part by a strong stromal foundation. We explore the link between stromal–epithelial crosstalk, paracrine communication, and the role of the keratinocyte growth factor (KGF) as a soluble mediator, underpinning the tissue-specific role of fibroblast subpopulations. Permeability studies adapted to a 96-well format allow for high throughput screening and demonstrate the role of the stromal compartment and tissue architecture on permeability and functionality, which is thought to be one of many factors responsible for unexpected drug outcomes using current approaches for pharmacokinetic testing. Full article

Exosomes are extracellular vesicles within the nanosized range that play roles in intercellular communication and thus have certain biological activities. The secretory signaling communication mechanism is an efficient way of exchanging information between cells and has been investigated as nature’s therapeutic drug carriers. This review will summarize the potential of exosomes as therapeutic tools and drug delivery vehicles for corneal pathologies. The cornea is an avascular ocular tissue, and its healing is a complex process including cell death and migration, cell proliferation and differentiation, and extracellular matrix remodeling. Here, we discussed the structure, barrier, phases, and healing cascade of cornea. We briefly reviewed the immunogenicity and toxicity of exosomes and role of exosomes in preserving cornea. Additionally, we provided combining exosome strategies with hydrogels, gene and stem cells therapy focused on corneal treatment, repair, and regeneration. Full article

Background: The histopathological assessment is critical in the comprehensive treatment process for patients diagnosed with oral squamous cell carcinoma (OSCC). A detailed and precise specimen characterization is essential to facilitate effective surgeon–pathologist communication. Methods: In response to this need, a user-friendly virtual communication protocol utilizing a 3D scanner has been developed. This study involved 50 patients with OSCC, whose resected tumors were directly scanned in the operating room and subsequently annotated and characterized using available software. Results: The direct application of annotations and descriptions onto the virtual tumor specimens significantly enhanced the quantity and accuracy of information conveyed to the pathologist. Conclusions: The proposed solution’s repeatability and standardized approach make integration into routine clinical practice feasible, thereby establishing a potential new standard in the field. Full article

The growing interest in plant-origin active molecules with medicinal properties has led to a revaluation of plants in the pharmaceutical field. Plant-derived extracellular vesicles (PDEVs) have emerged as promising candidates for next-generation drug delivery systems due to their ability to concentrate and deliver a plethora of bioactive molecules. These bilayer membranous vesicles, whose diameter ranges from 30 to 1000 nm, are released by different cell types and play a crucial role in cross-kingdom communication between plants and humans. Notably, PDEVs have demonstrated efficacy in treating various diseases, including cancer, alcoholic liver disease, and inflammatory bowel disease. However, further research on plant vesicles is necessary to fully understand their traits and purposes. This study investigates the phototoxic effects of extracellular vesicles (EVs) from Aloe arborescens, Aloe barbadensis, and Aloe chinensis on the human melanoma cell line SK-MEL-5, focusing on their anthraquinone content, recognized as natural photosensitizers. The phototoxic impact of Aloe EVs is associated with ROS production, leading to significant oxidative stress in melanoma cells, as validated by a metabolome analysis. These findings suggest that EVs from Aloe arborescens, Aloe barbadensis, and Aloe chinensis hold promise as potential photosensitizers, thus highlighting their potential for future application in photodynamic cancer therapy and providing valuable insights into the possible utilization of PDEVs for therapeutic purposes. Full article

The impressive achievements made in the last century in extending the lifespan have led to a significant growth rate of elderly individuals in populations across the world and an exponential increase in the incidence of age-related conditions such as cardiovascular diseases, diabetes mellitus type 2, and neurodegenerative diseases. To date, geroscientists have identified 12 hallmarks of aging (genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, impaired macroautophagy, mitochondrial dysfunction, impaired nutrient sensing, cellular senescence, stem cell exhaustion, defective intercellular communication, chronic inflammation, and gut dysbiosis), intricately linked among each other, which can be targeted with senolytic or senomorphic drugs, as well as with more aggressive approaches such as cell-based therapies. To date, side effects seriously limit the use of these drugs. However, since rejuvenation is a dream of mankind, future research is expected to improve the tolerability of the available drugs and highlight novel strategies. In the meantime, the medical community, healthcare providers, and society should decide when to start these treatments and how to tailor them individually. Full article

Osteoarthritis (OA) is a chronic disease affecting over 500 million people worldwide. As the population ages and obesity rates rise, the societal burden of OA is increasing. Pro-inflammatory cytokines, particularly interleukin-1β, are implicated in the pathogenesis of OA. Recent studies suggest that crosstalk between cartilage and synovium contributes to OA development, but the mechanisms remain unclear. Extracellular vesicles (EVs) were purified from cell culture-conditioned medium via ultracentrifugation and confirmed using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. We demonstrated that EVs were taken up by human synoviocytes and chondrocytes in vitro, while in vivo experiments revealed that fluorescent-labelled EVs injected into mouse joints were incorporated into chondrocytes and synoviocytes. EV uptake was significantly inhibited by dynamin-mediated endocytosis inhibitors, indicating that endocytosis plays a major role in this process. Additionally, co-culture experiments with HEK-293 cells expressing red fluorescent protein (RFP)-tagged CD9 and the chondrocytic cell line OUMS-27 confirmed the transfer of RFP-positive EVs across a 600-nm but not a 30-nm filter. These findings suggest that EVs from chondrocytes are released into joint fluid and taken up by cells within the cartilage, potentially facilitating communication between cartilage and synovium. The results underscore the importance of EVs in OA pathophysiology. Full article

This study investigated phytoplankton and water environmental factors in Yazhou Bay, South China Sea, during the winter, spring, and summer of 2023. It examined phytoplankton community structure, subgroup heterogeneity, and key environmental drivers. Phytoplankton abundance ranged from 0.08 to 14.30 × 10⁴ cells·L⁻¹, with high concentrations in estuary and nearshore zones. In summer, currents carry phytoplankton offshore, with stratification leading to high sedimentation in southern offshore waters. RDA results indicated that in winter and spring, inorganic nitrogen mainly influences phytoplankton distribution, while silicate is the primary factor in summer. Although seasonal differences in total phytoplankton abundance are minimal, significant horizontal and vertical distribution variations exist. Diverse preferences of different phytoplankton species for temperature, salinity, nitrogen, and phosphorus result in high species diversity. The Shannon–Wiener diversity index (H′) averages 3.96 ± 0.09, and the Pielou evenness index (J) averages 0.82 ± 0.01. Dominant species include Pseudo-nitzschia pungens, Skeletonema costatum, and Rhizosolenia sinica. Influenced by external oceanic water masses, estuary input, and islands, phytoplankton subgroups show regional and seasonal variations. Despite recorded harmful algal blooms (HABs) in adjacent waters, Yazhou Bay’s high biodiversity and low cell density suggest a low HAB risk, though future risks due to climate change and human activities remain. Full article

Microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in maintaining neural homeostasis but can also contribute to disease and injury when this state is disrupted or conversely play a pivotal role in neurorepair. One way that microglia exert their effects is through the secretion of small vesicles, microglia-derived exosomes (MGEVs). Exosomes facilitate intercellular communication through transported cargoes of proteins, lipids, RNA, and other bioactive molecules that can alter the behavior of the cells that internalize them. Under normal physiological conditions, MGEVs are essential to homeostasis, whereas the dysregulation of their production and/or alterations in their cargoes have been implicated in the pathogenesis of numerous neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), spinal cord injury (SCI), and traumatic brain injury (TBI). In contrast, MGEVs may also offer therapeutic potential by reversing inflammation or being amenable to engineering for the delivery of beneficial biologics or drugs. The effects of MGEVs are determined by the phenotypic state of the parent microglia. Exosomes from anti-inflammatory or pro-regenerative microglia support neurorepair and cell survival by delivering neurotrophic factors, anti-inflammatory mediators, and molecular chaperones. Further, MGEVs can also deliver components like mitochondrial DNA (mtDNA) and proteins to damaged neurons to enhance cellular metabolism and resilience. MGEVs derived from pro-inflammatory microglia can have detrimental effects on neural health. Their cargo often contains pro-inflammatory cytokines, molecules involved in oxidative stress, and neurotoxic proteins, which can exacerbate neuroinflammation, contribute to neuronal damage, and impair synaptic function, hindering neurorepair processes. The role of MGEVs in neurodegeneration and injury—whether beneficial or harmful—largely depends on how they modulate inflammation through the pro- and anti-inflammatory factors in their cargo, including cytokines and microRNAs. In addition, through the propagation of pathological proteins, such as amyloid-beta and alpha-synuclein, MGEVs can also contribute to disease progression in disorders such as AD and PD, or by the transfer of apoptotic or necrotic factors, they can induce neuron toxicity or trigger glial scarring during neurological injury. In this review, we have provided a comprehensive and up-to-date understanding of the molecular mechanisms underlying the multifaceted role of MGEVs in neurological injury and disease. In particular, the role that specific exosome cargoes play in various pathological conditions, either in disease progression or recovery, will be discussed. The therapeutic potential of MGEVs has been highlighted including potential engineering methodologies that have been employed to alter their cargoes or cell-selective targeting. Understanding the factors that influence the balance between beneficial and detrimental exosome signaling in the CNS is crucial for developing new therapeutic strategies for neurodegenerative diseases and neurotrauma. Full article

(1) Background: The purpose of this systematic review is to investigate the prevalent use of non-steroidal anti-inflammatory drugs (NSAIDs) in athletes and to comprehensively review the effectiveness and the results of these medications as it relates to injury management, training response, and overall sport performance. (2) Methods: An electronic literature search was performed in accordance with the recommendations and guidelines of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) protocol. A total of 7 randomized controlled studies met the review’s specific inclusion criteria from the 2250 studies initially identified within the PubMed database. (3) Results: In total, 346 adult female and male athletes from a variety of sporting activities and fitness levels were observed, of which 175 athletes were treated with either oral, topical, or local muscular infusion of an NSAID. Depending on study design, the outcomes focused on results obtained through physical exam findings, questionnaires, various performance metrics, and direct tissue sampling from microdialysis or biopsies. Across the 7 total studies, 2 articles focused on injured athletes and their varying pain responses with NSAIDs; 2 studies assessed the limited impact of NSAIDs on performance; and 3 articles revealed the use of NSAIDs correlating to no increases in either collagen synthesis or satellite cell activity after exercise. (4) Conclusions: The systematic review affirmed that NSAIDs can be effective for managing acute pain. However, their value appears to diminish when treating chronic injuries or if NSAIDs are expected to improve performance or have other ergogenic effects in athletes, as the aggregate data did not support such benefits. (5) Practical applications: NSAIDs can be beneficial for athletes in the right situation, but the fact that there are risks and possible disadvantageous results with their use highlights the importance of promoting appropriate expectations and the judicious use of these medications with the athletic community. Full article