Search Results (417)

The fungal component of microbiota, known as the mycobiome, inhabits different body niches such as the skin and the gastrointestinal, respiratory, and genitourinary tracts. Much information has been gained on the bacterial component of the human microbiota, but the mycobiome has remained somewhat elusive due to its sparsity, variability, susceptibility to environmental factors (e.g., early life colonization, diet, or pharmacological treatments), and the specific in vitro culture challenges. Functionally, the mycobiome is known to play a role in modulating innate and adaptive immune responses by interacting with microorganisms and immune cells. The latter elicits anti-fungal responses via the recognition of specific fungal cell-wall components (e.g., β-1,3-glucan, mannan, and chitin) by immune system receptors. These receptors then regulate the activation and differentiation of many innate and adaptive immune cells including mucocutaneous cell barriers, macrophages, neutrophils, dendritic cells, natural killer cells, innate-like lymphoid cells, and T and B lymphocytes. Mycobiome disruptions have been correlated with various diseases affecting mostly the brain, lungs, liver and pancreas. This work reviews our current knowledge on the mycobiome, focusing on its composition, research challenges, conditioning factors, interactions with the bacteriome and the immune system, and the known mycobiome alterations associated with disease. Full article

Patients undergoing epidermal growth factor receptor inhibitor (EGFRI) therapy frequently experience dermatologic side effects, notably papulopustular rash, which impacts 50–90% of recipients. This rash typically appears on the face, chest, and back within weeks of treatment, resembling acne but stemming from distinct pathophysiological mechanisms, causing significant discomfort and reduced quality of life. Prophylactic measures and symptom-based treatment are recommended, emphasizing patient education, topical agents, and systemic therapies for severe cases. A 41-year-old female with advanced colonic mucinous adenocarcinoma developed severe acneiform rash and pruritus during EGFRI therapy with panitumumab. Initial standard treatment with oral doxycycline was discontinued after two days due to severe gastrointestinal intolerance characterized by intense nausea and dyspepsia. With limited access to dermatological consultation, treatment with rose stem cell-derived exosomes (RSCEs) provided rapid symptom relief. Significant improvement was observed within 24 h, with complete resolution of pruritus and substantial reduction in inflammatory lesions within 72 h. RSCEs demonstrate anti-inflammatory effects through the modulation of pro-inflammatory cytokines including interleukin-6, interleukin-1β, and tumor necrosis factor-α, while promoting fibroblast proliferation and collagen synthesis enhancement. They may represent a possible alternative to corticosteroids, avoiding associated side effects such as skin atrophy, delayed wound healing, and local immunosuppression. This case underscores the potential of innovative treatments like RSCEs in managing EGFRI-induced skin complications when standard therapies are not tolerated, particularly in healthcare systems with limited dermato-oncological resources. Full article

Staphylococcus spp. skin colonization is involved in the pathogenesis of atopic dermatitis (AD). While coagulase-positive Staphylococcus aureus strains are known to worsen symptoms, the role of coagulase-negative staphylococci (CoNS) remains controversial. Further research is needed to clarify the pathogenicity of CoNS in AD patients. A study involving 329 children with AD (mean age: 4.89 years) assessed the frequency of staphylococcal colonization on affected skin, along with the toxin-producing properties and antibiotic resistance of isolated strains. Mild AD: Predominantly colonized by CoNS (especially S. epidermidis). Moderate/Severe AD: Showed a significant increase in S. aureus colonization. CoNS (including S. epidermidis) could produce enterotoxins (A, B, C) and toxic shock syndrome toxin-1 (TSST-1), though less frequently than S. aureus strains. In severe AD, the number of toxin-producing CoNS strains (especially enterotoxin A producers) was higher than in mild AD, and the number of non-toxin-producing strains was lower. CoNS exhibited higher resistance rates than S. aureus. Methicillin-resistant S. epidermidis (MRSE): 23.4%. Methicillin-resistant S. aureus (MRSA): 1.27%. CoNS may contribute to AD pathogenesis through toxin production (exacerbating inflammation) and antibiotic resistance (limiting treatment options). Severe AD may involve a synergistic effect between S. aureus and toxin-producing CoNS. Full article

Scaffold architecture plays a significant role in regulating cellular and microbial interactions in tissue engineering applications. This study evaluates the performance of 3D-printed poly (lactic acid) (PLA) scaffolds with varying porosity levels (20%, 40%, 60%, 80%, and 100%) in mechanical strength, supporting human skin fibroblast (HSF) viability and reducing bacterial colonization of Gram-positive bacteria (Staphylococcus epidermidis, Staphylococcus aureus), and Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli). The maximum tensile strength (28 MPa) was achieved in the 100% dense scaffold. Increasing porosity drastically decreased tensile strength, where 80% PLA scaffold possessed 16 MPa strength. At greater levels of porosity (60% and 40%), tensile strengths greatly decrease (8 MPa and 4 MPa), while ductility increases, especially at high porosity levels. HSF viability, assessed using the AlamarBlue assay, showed a time-dependent increase in cell proliferation, with the highest viability observed on scaffolds with 60% and 80% porosity. SEM imaging confirmed strong cell adhesion on the 80% porous scaffold, indicating that intermediate-to-high porosity enhances cell attachment and metabolic activity. In contrast, bacterial adhesion showed species-specific responses to scaffold porosity. S. epidermidis and E. coli exhibited a progressive increase in adherence with porosity, peaking at 100%. P. aeruginosa showed maximum adhesion at 80%, suggesting a porosity “sweet spot” that favors its colonization. S. aureus adhered most strongly to scaffolds with intermediate porosities (40–60%) and significantly less at 100% porosity. The current study provides insights into scaffold design considerations, emphasizing the need for optimized scaffold architecture that balances regenerative potential with infection control in tissue engineering applications. Full article

Acne is a highly prevalent skin condition with multifactorial pathophysiology, where Cutibacterium acnes (C. acnes) overgrowths generate inflammation. C. acnes can grow and adhere, through the formation of biofilms, to almost any surface, which enables chronic infections. Acne treatment with antibiotics can induce topical antimicrobial resistance, impair microbiome biodiversity and cause cutaneous dysbiosis. In this study, we assess the effect of a standardized propolis extract (PE) from Greece against C. acnes, whilst maintaining skin’s microbiome biodiversity, and we investigate its effect against genes related to the attachment and colonization of C. acnes, as well as against biofilm formation. The extract has been chemically characterized by GC-MS and was additionally tested for its antioxidant properties by the Folin–Ciocalteu method and the 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) assay and its regulatory activity on the expression of antimicrobial and anti-inflammatory genes in normal human epidermal keratinocytes (NHEKs). The suggested efficacy of PE in targeting pathogenic C. acnes biofilm, via downregulation of virulence genes, represents an alternative strategy to modulate the behavior of skin microbiota in acne, paving the way for next-generation acne-targeting products. Full article

Laminosioptes cysticola (Vizioli, 1870), a tissue-dwelling mite responsible for nodular acariasis in birds, was identified from two hens reared in a rural backyard flock in Umbria, Italy. Adult mites were found in the subcutaneous tissue and on the serosal surface of various internal organs. Larval and first- and second-stage nymphal forms were observed beneath the skin and near the trachea and esophageal serosa. By comparing the existing literature with that reported in the present study, we propose a hypothetical reconstruction of the parasite’s life cycle. It is postulated that the entry of L. cysticola occurs through the cervical skin, where adults mate and larviparous females give birth to larvae. These larvae migrate into the loose connective tissues surrounding the trachea and esophagus, where they develop into nymphs. The immature forms then progress along the esophagus and trachea to reach the thoracic and abdominal cavities, colonizing the serosal surfaces of visceral organs. It remains unclear whether, or how, the mites return to the subcutaneous tissues to complete their maturation. Senescent specimens degenerate within the subcutis, where they are encased by a granulomatous inflammatory reaction that leads to the formation of characteristic calcified nodules. Full article

Repairing and regenerating tissue barriers is a key challenge in regenerative medicine. Stem cells play a crucial role in restoring the structural and functional integrity of key epithelial barrier surfaces, including the skin and mucosa. This review analyzes the role of dental pulp stem cells (DPSCs) and their derivatives, including extracellular vesicles, conditioned medium, and intracellular factors, in accelerating skin wound healing. The key mechanisms include: (1) DPSCs regulating inflammatory microenvironments by promoting anti-inflammatory M2 macrophage polarization; (2) DPSCs activating vascular endothelial growth factor (VEGF) to drive angiogenesis; (3) DPSCs optimizing extracellular matrix (ECM) spatial structure through matrix metalloproteinase/tissue inhibitor of metalloproteinase (MMP/TIMP) balance; and (4) DPSCs enhancing transforming growth factor-β (TGF-β) secretion to accelerate granulation tissue formation. Collectively, these processes promote wound healing. In addition, we explored potential factors that accelerate wound healing in DPSCs, such as oxidative stress, mechanical stimulation, hypertension, electrical stimulation, and organoid modeling. In addition to demonstrating the great potential of DPSCs for skin repair, this review explores their translational prospects in mucosal regenerative medicine. It covers the oral cavity, esophagus, colon, and fallopian tube. Some studies have found that combining DPSCs and their derivatives with drugs can significantly enhance their biological effects. By integrating insights from skin and mucosal models, this review offers novel ideas and strategies for treating chronic wounds, inflammatory bowel disease, and mucosal injuries. It also lays the foundation for connecting basic research results with clinical practice. This represents a significant step forward in tackling these complex medical challenges and lays a solid scientific foundation for developing more targeted and efficient regenerative therapies. Full article

Background: In burn injuries, wound healing effectiveness is complex and influenced significantly by the local biochemical environment and the physicochemical properties of topical preparations. pH lesions modulation can influence protection barrier integrity, inflammatory responses, and microbial colonization. Their antioxidant, antimicrobial, and anti-inflammatory properties, of the topical formulations enriched with plant extracts have demonstrated promising results. Objective: The aim of the study was to develop and characterize topical oleogel and hydrogel formulations containing ethanolic and hydroalcoholic extracts of medicinal plants (Boswellia serrata, Ocimum basilicum, Sambucus nigra, and Galium verum), and to evaluate the impact of their physicochemical properties, rheological behavior, in contrast with the wound pH modulation, and healing efficacy in an experimental burn model. Methods: Second-degree burns were induced uniformly on Wistar rats using the validated RAPID-3D device. All formulations were applied daily for 21 days, and wound healing was assessed through several measurements specific to the wound surface, skin temperature, pH, and, last but not least, histological analyses. Formulations’ physicochemical and rheological properties, including pH, viscosity, and spreadability, were also analyzed and systematically characterized. Results: Oleogel formulations demonstrated superior wound healing performance compared to hydrogels. Formulations containing Boswellia serrata and Ocimum basilicum extracts significantly reduced wound size, inflammation, and melanin production by days 9 and 21 (p < 0.05). The beneficial outcomes correlated strongly with formulation acidity (pH < 6), high viscosity, and enhanced thixotropic behavior, indicating improved adherence and sustained bioactive compound release. Histological evaluations confirmed enhanced epithelialization and reduced inflammation. Conclusions: Particularly Boswellia serrata and Ocimum basilicum in oleogel formulations in ethanolic solvent effectively modulated wound pH, enhanced topical adherence, and improved burn wound healing. These findings highlight their potential clinical application and justify further clinical investigations. Full article

Candida auris is an emerging multidrug-resistant fungal pathogen with a high affinity for skin colonization and significant potential for nosocomial transmission. This study aimed to develop and evaluate chitosan-based hydrogels loaded with nystatin and propolis as a topical antifungal strategy for skin decolonization of C. auris. The formulations were selected based on our previous results and optimized for cutaneous application. The internal structure of the hydrogels was investigated by polarized light microscopy, confirming the amorphous nature of propolis and the partial dispersion of nystatin. The antifungal activity was assessed against ten fluconazole-resistant C. auris strains. The CS-NYS-PRO1 formulation demonstrated the highest antifungal performance in the agar test, also reducing viable cell counts to undetectable levels within 6 h. Time–kill assays and SEM imaging confirmed the rapid fungicidal effect and revealed severe membrane disruption and cytoplasmic leakage. Molecular docking analyses indicated the strong binding of nystatin to both sterol 14α-demethylase (CYP51) and dihydrofolate reductase (DHFR) from C. auris, suggesting complementary membrane and intracellular mechanisms of action. These findings support the use of such hydrogels as a local, non-invasive, and biocompatible strategy for managing C. auris colonization, with promising implications for clinical use in infection control and the prevention of skin-mediated transmission in healthcare settings. Full article

Multidrug-resistant (MDR) Mycoplasma genitalium (M. genitalium) presents a significant risk of treatment failure in many sexually transmitted infections (STIs) and can result in persistent and recurrent urethritis or cervicitis. This case report describes a recurrent M. genitalium urethritis resistant to sulfamethoxazole-trimethoprim (TMP-SMX), doxycycline, and moxifloxacin. The infection was ultimately cured after both the removal of a nidus of infection and through the use of Lefamulin. Lefamulin is a novel agent approved for use in community-acquired bacterial pneumonia and bacterial skin infections that may be useful in difficult sexually transmitted infections. Background/Objectives: Deciding whether or not to treat M. genitalium can be challenging as it can be a colonizer, or present with a symptomatic pathogen, and even if it is causing symptoms, it can be drug-resistant. Our objective here is to highlight important considerations on whether or not to treat and, if so, what options exist. Conclusions: In a world of increasing drug-resistant STIs, this case highlights the challenges of managing MDR M. genitalium and how foreign bodies can allow reoccurrence. Also highlighted in this case, Lefamulin appears to be a viable alternative line of treatment of MDR M. genitalium that defies other first-line antibiotics. Full article

Bloodstream infections (BSIs) are a major cause of morbidity and mortality in acute myeloid leukemia (AML) patients undergoing induction chemotherapy. Staphylococcus epidermidis, typically a skin commensal, is increasingly recognized as a pathogen in these vulnerable individuals. This study investigated whether genomic differences exist between infectious and gastrointestinal colonizing S. epidermidis isolates from AML patients and how these compare to colonizing and infectious isolates from other patient groups and biogeographic sites. We analyzed 114 isolates—44 from AML patients (23 infections, 21 GI colonizers) and 70 from public datasets (34 infections, 36 colonizers). Stool samples underwent 16S rRNA sequencing and culture to identify colonization, while bloodstream isolates were sequenced and compared. Genomic profiling using Roary, Scoary, Phyre2, and InterProScan revealed that infectious and GI-colonizing AML isolates were phylogenetically close but genomically distinct. Infectious isolates from AML patients were significantly enriched for resistance genes (e.g., mecA, mecR1, mecI, ANT(4′)-Ib) and the biofilm-associated gene icaA. AML infectious isolates harbored more resistance genes and mobile elements than non-AML strains but lacked widespread classical virulence factors. These results suggest that S. epidermidis pathogenicity in immunocompromised hosts is driven by genomic adaptability and antibiotic tolerance rather than traditional virulence mechanisms. Full article

Dermatophytosis is a fungal infection that affects the skin, hair, and nails, impacting approximately 25% of the global population. Nannizzia gypsea is a geophilic fungus that can cause infections in humans and animals. Several studies have been conducted regarding its virulence, or ability to cause disease. This species may produce keratinolytic enzymes and form biofilms, which can increase resistance to treatment. Thus, this study focuses on investigating the biofilm formation of N. gypsea isolated from canine dermatophytosis using an ex vivo hair model, its biofilm extracellular matrix macromolecular contents, and the expression of genes involved in the colonization of keratinized surfaces. The biofilm was analyzed for metabolic activity using the XTT reduction assay, crystal violet staining to measure biofilm biomass, scanning electron microscopy (SEM), and the presence of polysaccharides, proteins, and extracellular DNA in the biofilm extracellular matrix. The virulence genes subtilisin 7, fungalysin (extracellular metalloproteinase), and efflux pump (Multidrug and Toxin Extrusion Protein 2) were evaluated by qPCR, comparing the planktonic and biofilm phenotypes. N. gypsea formed a robust biofilm, which matured after 5 days. Scanning electron microscopy (SEM) revealed the presence of an extensive extracellular matrix. In the hair model, the characteristic ectothrix parasitism of the species is observable. The gene expression analysis revealed a higher expression of all evaluated genes in the biofilm form compared to the planktonic form. Thus, N. gypsea exhibits a biofilm characterized by a robust extracellular matrix and high gene expression of factors related to pathogenesis and resistance. Full article

Cardiovascular disease (CVD) is the most common non-cancer cause of death among cancer survivors. Lifestyle and clinical factors associated with cancer mortality are also associated with cardiovascular mortality. The American Heart Association (AHA) has termed these factors “cardiovascular health” (CVH), using Life’s Simple 7 (LS7) or “Life’s Essential 8 (LE8)” to determine poor, intermediate, and high (ideal) CVH. Further, less than ideal CVH is associated with higher cancer mortality. Yet, CVH among cancer survivors remains understudied. This systematic review examined the extant literature, providing a comprehensive report of the findings addressing CVH among cancer survivors. Methods: Using PRISMA guidelines, we systematically examined CVH among cancer survivors (including patients) within PubMed, Scopus, CINAHL, and Embase databases without date limitations from June 2024 to December 2024 using the following keywords: “cancer survivors”, “cancer patient”, “cardiovascular health”, and “cardiovascular risk factors”. Two reviewers independently accessed articles in concordance with LS7 and LE8 metrics. The included studies were examined and assessed for risk of bias and synthesized to elucidate themes of CVH among cancer survivors. Results: We retrieved 2935 studies examining breast, gynecological, endometrial, prostate, colon, lung, lymphoma, and skin cancer survivors published from 2002–2024. Overall, 10 studies met criteria utilizing LS7 or LE8 CVH health outcomes (4 LS7, 5 LE8, and 1 LS7/LE8), ages 40–70 years, with a population (n = 35,980) consisting of mostly female, non-Black individuals; mean survivorship was 7.2 years. Four themes emerged: CVH outcomes among cancer survivors, social factors impacting CVH outcomes, associations of CVH, and other health outcomes opportunities for CVH awareness. Conclusions: We found that cancer survivors frequently report less than ideal CVH outcomes and would benefit from education/empowerment to support lifestyle changes that improve CVH. Full article

Background/Objectives: Patients with inflammatory bowel disease (IBD) are at an increased risk of various cancers; such as colorectal cancer; skin cancer; bile duct cancer; or lymphoma; with IBD itself not being the sole cause. Inappropriate or ineffective IBD therapy with a continuous inflammatory burden within the gut leads to an increased risk of malignancy. Our study aimed to investigate the risk of malignancy in our patient cohort; focusing on concomitant therapy; disease duration; and inflammatory burden. Methods: A total of 333 consecutive adult patients with IBD (Crohn’s disease; ulcerative colitis; and IBD unclassified) were included in this study. Data from patients were collected retrospectively using patient charts. The patients were treated in the gastroenterological outpatient clinic of the University Hospital of Augsburg; Germany; between 1 January 2014 and 31 December 2018. Results: The study group included 333 patients; 32 (9.61%) of whom suffered from malignancy (any form). Men (n = 21; 65.62%) tended to develop malignancy more often than women (n = 11; 34.38%, p = 0.051). It was also observed that the probability of developing cancer was 2.40 times higher in male patients than in female patients in our cohort. However, this trend was non-significant (HR = 2.412; p = 0.075). Furthermore; the probability of developing cancer increased with the increasing age at the time of the first diagnosis of IBD (HR = 1.088; p < 0.025). A total of 20 patients (6.00%) received their cancer diagnosis after being diagnosed with IBD. The majority of those patients had skin (n = 6; 30.00%) or colon cancer (n = 5; 25.00%). Other diseases such as CML; NHL; HL; HCC; liver sarcoma; prostate cancer; breast cancer; seminoma; thyroid cancer (a second cancer in one of the patients); or CUP syndrome/lung cancer were diagnosed in single patients. Patients with IBD and colon cancer (n = 5; 25.00%) shared some of the known risk factors for tumour development; such as a long-lasting IBD (n = 5; 100.00%), diagnosis at a young age (under 30; n = 3; 60.00%), and the coexistence of PSC (n = 1; 20.00%). The cancer prevalence rate was relatively low in our cohort despite the use of diverse biologics and immunosuppressive drugs. Faecal calprotectin was confirmed as a relevant tool for inflammation monitoring in this cohort. Conclusions: In our study cohort; we could show a low prevalence rate of malignancy in IBD. There were more malignancies in men and in patients who were diagnosed with IBD at later ages. It can be observed that the prevalence rate of cancer was relatively low despite the use of diverse biologics and immunosuppressive drugs; which is the major conclusion of this study. Additionally; the known correlation between elevated levels of faecal calprotectin and gut inflammation was confirmed through our statistical analysis. The use of calprotectin as a non-invasive screening tool for gut inflammation is advised. Full article

The genus Pistacia from the Anacardiaceae family contains species of wild flowering plants. The only species that produces edible nuts large enough for commercial sale is P. vera L. (pistachio). Other species, such as P. terebinthus L., P. atlantica L., and P. khinjuk, are used as pistachio rootstocks. Pistacia species include phenolic compounds, such as flavonoids, essential oils, and tannins, which are responsible for a number of pharmacological properties. The species most commonly investigated for their anticancer and/or cytotoxic activities against cancer cells in experimental studies include P. lentiscus, P. atlantica subspecies, and P. chinensis subsp. integerrima. However, no review exists that evaluates the phenolic compounds of three other Pistacia species (P. vera L., P. terebinthus L., and P. khinjuk) and their anticancer and cytotoxic effects. Thus, this review aims to thoroughly assess the phenolic compounds that were isolated from these species and investigate any potential anticancer or cytotoxic effects on cancer cells. The findings show that pistacia species and their isolated phenolic compounds (phenolic acids, flavonoids, and essential oils) from different plant parts have anticancer activity against lung, cervical, prostate, gastric, colon, liver, renal, skin, and breast cancer cells. Additionally, certain phenolic compounds from pistacia species have cytotoxic activity; however, the degree of toxicity may vary based on the dosage and duration of use. Further experiments are required to fully understand the possible mechanisms underlying the anticancer and cytotoxic effects of pistacia species and their phenolic compounds on cancer cells. Full article