Search Results (907)

Schaalia canis is a Gram-positive, facultatively anaerobic, rod-shaped bacterium originally isolated from the mucosa and skin of dogs. While it is a part of the normal canine oral flora, it has rarely been implicated in human disease, with only one prior case of cellulitis reported following a dog bite. Case Presentation: We present the case of a 57-year-old immunocompetent man who developed osteomyelitis of the left index finger following a delayed presentation after a dog bite. Despite initial conservative management with empirical oral antibiotics, the infection progressed, eventually requiring surgical debridement and the terminalisation of the finger at the proximal interphalangeal joint. Cultures from intraoperative bone specimens yielded the growth of Schaalia canis, with no other pathogenic organisms identified on the extended culture. Conclusions: This is the first documented case of Schaalia canis-associated osteomyelitis in a human and the first to necessitate a surgical intervention, expanding the known clinical spectrum of this organism. This case underscores the risks of delayed intervention in polymicrobial animal bite wounds and highlights the emerging role of Schaalia species as opportunistic zoonotic pathogens, particularly in the setting of deep, refractory infections. Full article

Human adipose-derived stem cells (hASCs) are widely used in regenerative medicine due to their accessibility and high proliferative capacity. Platelet lysate (PL) has recently emerged as a promising alternative to fetal bovine serum (FBS), offering superior cell expansion potential; however, the molecular basis for its efficacy remains insufficiently elucidated. In this study, we performed RNA sequencing to compare hASCs cultured with PL or FBS, revealing a significant upregulation of genes related to stress response and cell proliferation under PL conditions. These findings were validated by RT–qPCR and supported by functional assays demonstrating enhanced cellular resilience to oxidative and genotoxic stress, reduced doxorubicin-induced senescence, and improved antiapoptotic properties. In a murine wound model, PL-treated wounds showed accelerated healing, characterized by thicker dermis-like tissue formation and increased angiogenesis. Immunohistochemical analysis further revealed elevated expression of chk1, a DNA damage response kinase encoded by CHEK1, which plays a central role in maintaining genomic integrity during stress-induced repair. Collectively, these results highlight PL not only as a viable substitute for FBS in hASC expansion but also as a bioactive supplement that enhances regenerative efficacy by promoting proliferation, stress resistance, and antiaging functions. Full article

Although cold atmospheric plasma (CAP) has shown promise in facilitating wound repair due to its non-thermal and non-invasive properties, its dynamic effects on cellular response and metabolic regulation remain poorly characterized, and the mechanism is still unclear. In this study, we developed a microfluidic experimental system that integrates a CAP treatment module with multiparametric in situ sensing capabilities, along with precise environmental control of temperature, humidity, and CO₂ concentration. A stratified microfluidic chip was engineered to co-culture HaCaT keratinocytes and HSF fibroblasts. CAP treatment was applied within this platform, and the dynamic processes of cell migration, proliferation, and multiple metabolic markers were simultaneously monitored. The experimental results show that the system can not only achieve real-time observation in the healing process under plasma intervention, but also find that the healing process is closely related to the concentration of NO₂⁻. In addition, the study also found that keratin KRT14, which is thought to be closely related to wound healing, decreased significantly in the process of plasma-induced healing. The platform provides high-resolution experimental tools to elucidate the biological effects of CAP and has the potential for parameter optimization, material evaluation, and personalized therapeutic development to advance plasma research and clinical translational applications. Full article

Background/Objectives: Chronic wounds represent a significant clinical and public health challenge due to impaired tissue repair and high associated morbidity. This study investigates the therapeutic potential of the secretome derived from human mesenchymal stem cells obtained from the pulp of deciduous teeth (hDP-MSCs) in promoting skin wound healing. Methods: After confirming the mesenchymal identity and multipotent differentiation potential of hDP-MSCs by using flow cytometry and histological staining, the effects of the secretome on human keratinocyte (HaCaT) cultures were evaluated. Results: Scratch assays, performed under high- and low-glucose conditions, demonstrated that the secretome significantly promoted keratinocyte migration and wound closure without compromising cell viability. Additionally, the secretome modulated the expression of key genes involved in inflammation and tissue regeneration, including IL-1β, TNF-α, TGF-β1, and VEGF-α, in a time-dependent manner. Under inflammatory conditions induced by lipopolysaccharide, co-treatment with the secretome significantly reduced TNF-α expression and increased TGF-β1 expression, suggesting an anti-inflammatory effect. Conclusions: These findings indicate the potential of the hDP-MSC-derived secretome as a promising cell-free therapeutic strategy capable of accelerating skin regeneration and modulating the inflammatory response during the wound healing process. Full article

In familial Alzheimer’s disease (FAD), presenilin 1 (PSEN1) E280A cholinergic-like neurons (ChLNs) induce aberrant secretion of extracellular amyloid beta (eAβ). How PSEN1 E280A ChLNs-eAβ affects microglial activity is still unknown. We obtained induced microglia-like cells (iMG) from human peripheral blood cells (hPBCs) in a 15-day differentiation process to investigate the effect of bolus addition of Aβ42, PSEN1 E280A cholinergic-like neuron (ChLN)-derived culture supernatants, and PSEN1 E280A ChLNs on wild type (WT) iMG, PSEN1 E280A iMG, and sporadic Alzheimer’s disease (SAD) iMG. We found that WT iMG cells, when challenged with non-cellular (e.g., lipopolysaccharide, LPS) or cellular (e.g., Aβ42, PSEN1 E280A ChLN-derived culture supernatants) microenvironments, closely resemble primary human microglia in terms of morphology (resembling an “amoeboid-like phenotype”), expression of surface markers (Ionized calcium-binding adapter molecule 1, IBA-1; transmembrane protein 119, TMEM119), phagocytic ability (high pHrodo™ Red E. coli BioParticles™ phagocytic activity), immune metabolism (i.e., high generation of reactive oxygen species, ROS), increase in mitochondrial membrane potential (ΔΨm), response to ATP-induced transient intracellular Ca²⁺ influx, cell polarization (cluster of differentiation 68 (CD68)/CD206 ratio: M1 phenotype), cell migration activity according to the scratch wound assay, and especially in their inflammatory response (secretion of cytokine interleukin-6, IL-6; Tumor necrosis factor alpha, TNF-α). We also found that PSEN1 E280A and SAD iMG are physiologically unresponsive to ATP-induced Ca²⁺ influx, have reduced phagocytic activity, and diminished expression of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) protein, but when co-cultured with PSEN1 E280A ChLNs, iMG shows an increase in pro-inflammatory phenotype (M1) and secretes high levels of cytokines IL-6 and TNF-α. As a result, PSEN1 E280A and SAD iMG induce apoptosis in PSEN1 E280A ChLNs as evidenced by abnormal phosphorylation of protein TAU at residue T205 and cleaved caspase 3 (CC3). Taken together, these results suggest that PSEN1 E280A ChLNs initiate a vicious cycle between damaged neurons and M1 phenotype microglia, resulting in excessive ChLN death. Our findings provide a suitable platform for the exploration of novel therapeutic approaches for the fight against FAD. Full article

Cat bites frequently lead to polymicrobial infections due to deep puncture wounds that inoculate oral flora into poorly oxygenated tissues. While Pasteurella multocida is the most commonly implicated organism, environmental and atypical pathogens may also play a role, yet often go unrecognized. This article reports a rare case of polymicrobial septic arthritis caused by a domestic cat bite in an immunocompetent adult, with isolation of Rahnella aquatilis, a freshwater-associated Enterobacterales species not previously reported in this context. A 33-year-old immunocompetent male presented with acute hand swelling, pain, and functional impairment within 24 h of the bite. Emergency surgery revealed purulent tenosynovitis and arthritis. Intraoperative cultures identified R. aquatilis, P. multocida, and Pantoea agglomerans. Identification was performed using MALDI-TOF MS. The R. aquatilis isolate was susceptible to beta-lactams (excluding ampicillin), quinolones, and co-trimoxazole. The patient received amoxicillin–clavulanic acid and fully recovered within two weeks. This is the first reported case of joint infection involving R. aquatilis following a cat bite. It highlights the importance of considering environmental Enterobacterales in animal bite wounds, and the utility of advanced microbiological tools for detecting uncommon pathogens. Broader awareness may improve diagnosis and guide targeted therapy in polymicrobial infections. Full article

New stable three-dimensional hydrogels were obtained in an inert gas atmosphere in light in an aqueous dispersion of the main components: cod collagen, methyl methacrylate, polyethylene glycol, RbTe_1.5W_0.5O₆ complex oxide, and modifying additives. The analysis of the new hydrogels’ cytotoxicity using the MTT assay showed that the cytotoxicity of the sample extracts was observed in a number of examples, but was decreased with increasing dilution of the extracts. The decrease in cell viability at high concentrations of the extract is likely caused by a decrease in the number of specific components of the complete culture medium used to produce extracts. It is related to the well-known adsorption of medium proteins by the gel component, high-molecular compounds included in the matrix. The stimulating effect of the substances included in its composition was observed with a significant dilution of the extract, i.e., the proliferative activity of the cells increased. The extract of the hydrogel hydrolysate sample and all its dilutions did not show cytotoxicity in the MTT assay examples. It determines the prospect of its use on the wound surface, since hydrogel destruction occurs under the action of body enzymes. The new hydrogel is a promising material for creating wound coverings or scaffolds. Full article

Beyond its immunological role, colostrum has emerged as a promising, non-invasive source of bioactive factors, including mesenchymal stem/stromal cells (MSCs). This study represents the first attempt to isolate and characterize MSCs from equine colostrum (C-MSCs) to assess their potential use in veterinary regenerative medicine. Colostrum (n = 6) was collected from mares immediately after their delivery and centrifuged, and the recovered cells were cultured under standard conditions. The C-MSCs displayed plastic adherence and a heterogeneous morphology, including spindle-shaped and epithelial-like cells. The population doubling time (PDT) values varied among the samples, and four out of six showed rapid proliferation (<2 days). Colony-forming unit (CFU) assays confirmed their clonogenic potential, though significant inter-sample variability was observed (p < 0.05). Spheroid formation assays revealed differences in cell–cell adhesion: four out of six samples formed stable spheroids within four days. A migration assay showed significant variability (p < 0.05): one out of six achieved complete wound closure within 72 h, whereas five out of six reached ~30% at 96 h. All samples were positive for adipogenic, chondrogenic, and osteogenic differentiation as shown via staining. RT-PCR confirmed MSC marker expression, while hematopoietic markers were absent. MHC-I expression was weak in five out of six samples, whereas MHC-II was consistently negative. These findings support equine colostrum as a viable MSC source, though its variability requires further validation with larger samples. Additional research is needed to investigate C-MSCs’ immunomodulatory properties and therapeutic potential. Full article

This essay examines two hybrid poetic texts that emerged from a period of feminist activism in U.S. and global poetry communities from 2014 to 2017: the collaboratively, anonymously authored “No Manifesto” (2015) and the radically revised second edition of the book of poetry and visual art YOU DA ONE by Jennif(f)er Tamayo. “No Manifesto” and YOU DA ONE embrace the hybrid tactics of collectivity, incongruity, and nonresolution as ways of protesting sexism and sexual violence in poetry communities. Synthesizing theories of hybridity from poetry criticism as well as immigrant and borderlands studies, the essay defines hybridity as a literary representation of cultural positions forcefully imposed upon subjects. Born out of the domination of sexual and state violence, hybridity marks the wound that remakes the subject, who develops strategies for resistance. By refusing to play by the rules of poetic or social discourse—the logics of domination that would have them be singular, cohesive, and compliant—Tamayo and the authors of “No Manifesto” insist on alternative ways of performing activism, composing literature, and entering the public sphere. These socially engaged, hybrid poetic texts demonstrate the power of the collective to disrupt the social and literary status quo. Full article

In this study, we integrated HSQC-based DeepSAT with UPLC-MS/MS to guide the isolation of omega-3 polyunsaturated fatty acid derivatives (PUFAs) from marine resources. Through this approach, four new (1–4) and nine known (5–13) PUFA analogues were obtained from large-scale cultures of the marine dinoflagellate Prorocentrum lima, with lipidomic profiling identifying FA18:5 (5), FA18:4 (7), FA22:6 (8), and FA22:6 methyl ester (11) as major constituents of the algal oil extract. Structural elucidation was achieved through integrated spectroscopic analyses of IR, 1D and 2D NMR, and HR-ESI-MS data. Given the pivotal role of microglia in Alzheimer’s disease (AD) pathogenesis, we further evaluated the neuroprotective potential of these PUFAs by assessing their regulatory effects on critical microglial functions in human microglia clone 3 (HMC3) cells, including chemotactic migration and amyloid-β42 (Aβ42) phagocytic clearance. Pharmacological evaluation demonstrated that FA20:5 butanediol ester (1), FA18:5 (5), FA18:4 (7), FA22:6 (8), and (Z)-10-nonadecenoic acid (13) significantly enhanced HMC3 migration in a wound-healing assay. Notably, FA18:4 (7) also significantly promoted Aβ42 phagocytosis by HMC3 microglia while maintaining cellular viability and avoiding pro-inflammatory activation at 20 μM. Collectively, our study suggests that FA18:4 (7) modulates microglial function in vitro, indicating its potential to exert neuroprotective effects. Full article

Background: Oral wound healing is a complex process influenced by extracellular matrix (ECM) remodeling and cellular migration. Hyaluronic acid (HA) and spermidine (SP) have shown regenerative potential, but their combined effects on oral tissues remain unexplored. This study aimed to characterize the effect of a gel composed of a mixture of HA and SP on the epithelial and connective compartments of oral tissue separately, evaluating (i) collagen turnover and cell migration on primary human gingival fibroblasts (HGFs) and (ii) epithelial integrity and cell proliferation on gingival organotypic cultures (OCs). Methods: HGFs were cultured, treated with HA-SP gel (1:0.5 HA-SP ratio) and evaluated for collagen types I and III (COL-I, COL-III), matrix metalloproteinase (MMP-1) protein and tissue inhibitor of MMP-1 (TIMP-1) levels secreted by the cells upon gel treatment, compared to CT. HGFs were also analyzed through a wound healing assay. Gingival samples were obtained to set OCs and were treated with different HA-SP formulations (HA 0.2%; 1:0.5 HA-SP ratio; 1:5 HA-SP ratio) to evaluate the beneficial addition of SP to HA for epithelial tissue. OC samples were formalin-fixed and paraffin-embedded and were stained with hematoxylin and eosin and immunostained for Ki-67 analysis. Results: In HGFs, the gel induced increased COL-III gene expression relative to that of COL-I after 48 h and stimulated cell migration, in turn favoring connective tissue remodeling and repair. In OCs, the gel preserved epithelial integrity up to 48 h, with the best effects observed with the 1:0.5 HA-SP ratio. After 72 h, epithelial detachment was more evident in HA formulations, suggesting that SP contributes to epithelial integrity. Conclusions: The HA-SP gel may support oral tissue healing by modulating ECM remodeling and maintaining epithelial integrity. The gel containing HA and SP at the 1:0.5 ratio may provide a promising solution for enhancing wound healing. Full article

Human gingival fibroblasts (HGnFs) play crucial roles in periodontal wound healing. This in vitro study examined the impact of varying concentrations of topical oxygen fluid (blue^®m) on HGnF morphology, viability, proliferation, oxidative stress and pro-inflammatory cytokine production. The attempt was to underscore the potential of blue^®m as a less cytotoxic alternative to chlorhexidine in the context of tissue-regeneration improvement. Primary HGnF cell cultures were subjected to oxygen fluid (blue^®m) at concentrations of 0.6, 1.2 and 2.4% for a duration of 1 min. The positive control was 0.12% chlorhexidine. Cell morphology as well as actin cytoskeleton were assessed using microscopy and immunofluorescence staining. Cell viability and proliferation were assessed through AlamarBlue and trypan blue assays at 1, 2, 7, 10 and 14 days. Levels of reactive oxygen species (ROS) were quantified using DCFH-DA assay. Pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, MMP-8 and TIMP-1) were assessed through ELISA. HGnF morphology and actin structure were preserved at all oxygen fluid concentrations. Cell viability and proliferation were significantly higher in the 0.6% and 1.2% groups than in the control and chlorhexidine groups (p ≤ 0.05). ROS levels were low at 0.6% and 1.2%, but increased at 2.4% and with chlorhexidine (p ≤ 0.05). Oxygen treatment reduced IL-1β, IL-6, TNF-α and TIMP-1 expression, while MMP-8 levels increased. Chlorhexidine significantly upregulated the expression of all proinflammatory cytokines (p ≤ 0.01). Oxygen fluid (blue^®m) therapy improves the viability and proliferation of gingival fibroblasts and offers anti-inflammatory and preliminary antioxidative effects at the cellular level, especially at lower concentrations (0.6% and 1.2%), indicating potential application in periodontal wound management, subject to clinical validation. Full article

Background/Objectives: Rho-associated coiled-coil-containing protein kinase inhibitors (ROCKis) have now become known as modulators of corneal endothelial wound repair and cell survival. However, evidence remains fragmented across laboratory and clinical reports. We performed a systematic review to synthesize preclinical and clinical data on ROCKis in corneal disease, assess their efficacy and safety, and identify research gaps. Methods: We searched PubMed, Web of Science, Scopus, and Google Scholar (until May 2025) for English-language original studies evaluating ROCKis in corneal models or patients. Inclusion criteria encompassed in vitro, ex vivo, in vivo, and clinical trials reporting functional outcomes (endothelial cell density, wound closure, visual acuity). Results: Thirty-one studies met criteria: 14 preclinical studies and 17 clinical studies. Preclinical models (rabbit, porcine, human explants) uniformly showed ROCKis (Y-27632, Ripasudil, Netarsudil, H-1152) accelerate corneal endothelial cell proliferation, migration, and restoration of a hexagonal monolayer with improved barrier and pump function over days to weeks. In 17 clinical investigations, topical Ripasudil or Netarsudil and cultured cell injections achieved significant corneal thinning, endothelial cell density and central corneal thickness changes, and visual acuity improvements (≥2 lines) with minimal adverse events. Overall bias was moderate in non-randomized studies and low in the RCTs. Conclusions: ROCKis demonstrate consistent pro-regenerative effects on corneal endothelium in multiple models and show promising clinical efficacy in Fuchs endothelial dystrophy and pseudophakic endothelial failure. Future work should explore novel delivery systems and larger controlled trials to optimize dosing, safety, and long-term outcomes. Full article

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory condition of the gastrointestinal tract. It is generally accepted that IBD is characterized by an inappropriate immune response to the intestinal microbiome in genetically susceptible individuals. Despite the available treatment options ranging from salicylates and corticosteroids, to immunosuppressants and biologics, there is still a high unmet medical need for patients who respond poorly to drugs or are not able to tolerate them. Microbiome-based therapeutics offer a valid treatment strategy for IBD with enhanced safety. A butyrate-producing consortium of six commensal strains (MH002) was evaluated in a series of in vitro, ex vivo, and in vivo experiments mimicking multiple IBD-related dysfunctions, namely disrupted intestinal permeability and immune activation. MH002 rapidly produced high levels of butyrate in fed-batch cultures, and significantly increased butyrate levels within one day after administration to IBD-derived gut microbial communities in vitro. Both in Caco-2/peripheral blood mononuclear cells (PBMCs) co-cultures, and IBD patients-derived organoids and colonic explants, MH002 reduced inflammation and restored epithelial barrier integrity. In addition, MH002 promoted wound repair in vitro. Finally, MH002 protected mice and rats from chemically induced colitis. Altogether, results showed that MH002 presents a novel therapeutic avenue for the treatment of IBD. Full article

The spore-forming probiotic Bacillus coagulans JBI-YZ6.3 interacts with the gut epithelium via its secreted metabolites as well as its cell walls, engaging pattern-recognition receptors on the epithelium. We evaluated its effects on human T84 gut epithelial cells using in vitro co-cultures, comparing metabolically active germinated spores to the isolated metabolite fraction and cell wall fraction under unstressed versus inflamed conditions. Germinated spores affected epithelial communication via chemokines interleukin-8, interferon gamma-induced protein-10, and macrophage inflammatory protein-1 alpha and beta after 2 and 24 h of co-culture. Non-linear dose responses confirmed that bacterial density affected the epigenetic state of the epithelial cells. In contrast, the cell wall fraction increased cytokine and chemokine levels under both normal and inflamed conditions, demonstrating that the intact bacterium had anti-inflammatory properties, regulating pro-inflammatory signals from its cell walls. During recovery from mechanical wounding, germinated spores accelerated healing, both in the absence and presence of LPS-induced inflammation; both the metabolite and cell wall fractions contributed to this effect. The release of zonulin, a regulator of tight junction integrity, was reduced by germinated spores after 2 h. These findings suggest that B. coagulans JBI-YZ6.3 modulates epithelial chemokine signaling, supports barrier integrity, and enhances epithelial resilience, highlighting its potential as an efficacious multi-faceted probiotic for gut health. Full article