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Experimental Eye Research Jul 2024Fungal keratitis (FK) is an infectious keratopathy can cause serious damage to vision. Its severity is related to the virulence of fungus and response of inflammatory....
Fungal keratitis (FK) is an infectious keratopathy can cause serious damage to vision. Its severity is related to the virulence of fungus and response of inflammatory. Rosmarinic acid (RA) extracted from Rosmarinus officinalis exhibits antioxidant, anti-inflammatory and anti-viral properties. The aim of this study was to investigate the effect of RA on macrophage autophagy and its therapeutic effect on FK. In this study, we demonstrated that RA reduced expression of proinflammatory cytokine, lessened the recruitment of inflammatory cells in FK. The relative contents of autophagy markers, such as LC3 and Beclin-1, were significantly up-regulated in RAW 264.7 cells and FK. In addition, RA restored mitochondrial membrane potential (MMP) of macrophage to normal level. RA not only reduced the production of intracellular reactive oxygen species (ROS) but also mitochondria ROS (mtROS) in macrophage. At the same time, RA induced macrophage to M2 phenotype and down-regulated the mRNA expression of IL-6, IL-1β, TNF-α. All the above effects could be offset by the autophagy inhibitor 3-Methyladenine (3-MA). Besides, RA promote phagocytosis of RAW 264.7 cells and inhibits spore germination, biofilm formation and conidial adherence, suggesting a potential therapeutic role for RA in FK.
Topics: Depsides; Rosmarinic Acid; Animals; Autophagy; Aspergillus fumigatus; Mice; Aspergillosis; Eye Infections, Fungal; Macrophages; Cinnamates; Reactive Oxygen Species; Membrane Potential, Mitochondrial; Keratitis; Disease Models, Animal; RAW 264.7 Cells; Cytokines; Phagocytosis
PubMed: 38797260
DOI: 10.1016/j.exer.2024.109944 -
Redox Biology Jul 2024Fungal keratitis is a severely vision-threatening corneal infection, where the prognosis depends on both fungal virulence and host immune defense. Inappropriate host...
Fungal keratitis is a severely vision-threatening corneal infection, where the prognosis depends on both fungal virulence and host immune defense. Inappropriate host responses can induce substantial inflammatory damage to the cornea. Therefore, in the treatment of fungal keratitis, it is important to concurrently regulate the immune response while efforts are made to eliminate the pathogen. Ebselen is a widely studied organo-selenium compound and has been demonstrated to have antifungal, antibacterial, anti-inflammatory, and oxidative stress-regulatory properties. The effectiveness of ebselen for the treatment of fungal keratitis remains unknown. In this study, ebselen was demonstrated to produce a marked inhibitory effect on Aspergillus fumigatus (A. fumigatus), including spore germination inhibition, mycelial growth reduction, and fungal biofilm disruption. The antifungal activity of ebselen was related to the cell membrane damage caused by thioredoxin (Trx) system inhibition-mediated oxidative stress. On the contrary, ebselen enhanced the antioxidation of Trx system in mammalian cells. Further, ebselen was proven to suppress the expressions of inflammatory mediators (IL-1β, IL-6, TNF-α, COX-2, iNOS, and CCL2) and reduce the production of oxidative stress-associated indicators (ROS, NO, and MDA) in fungi-stimulated RAW264.7 cells. In addition, ebselen regulated PI3K/Akt/Nrf2 and p38 MAPK signaling pathways, which contributed to the improvement of inflammation and oxidative stress. Finally, we verified the therapeutic effect of ebselen on mouse fungal keratitis. Ebselen improved the prognosis and reduced the fungal burden in mouse corneas. Expressions of inflammatory mediators, as well as the infiltration of macrophages and neutrophils in the cornea were also obviously decreased by ebselen. In summary, ebselen exerted therapeutic effects by reducing fungal load and protecting host tissues in fungal keratitis, making it a promising treatment for fungal infections.
Topics: Organoselenium Compounds; Isoindoles; Animals; Keratitis; Mice; Oxidative Stress; Azoles; Antifungal Agents; Anti-Inflammatory Agents; RAW 264.7 Cells; Antioxidants; Aspergillus fumigatus; Aspergillosis; Eye Infections, Fungal; Disease Models, Animal
PubMed: 38796864
DOI: 10.1016/j.redox.2024.103206 -
Orbit (Amsterdam, Netherlands) May 2024A 79-year-old female presented to the emergency department for sudden-onset ocular pain, edema, and erythema around her left eye. She also had a left-sided migraine and...
A 79-year-old female presented to the emergency department for sudden-onset ocular pain, edema, and erythema around her left eye. She also had a left-sided migraine and frontal fullness for 2 weeks. She had attentive care for the diagnosis of orbital cellulitis and prompt recognition of necrotizing fasciitis. Wound cultures were positive for over 5 strains of bacteria in addition to . In a combined effort by our institution's Ophthalmology and Otolaryngology departments, the patient was successfully treated with debridement, porcine bladder matrix, antibiotics, and antifungals. The authors describe the first reported case of eyelid and periorbital necrotizing fasciitis, caused by mixed flora and , that showed promising wound healing with the outlined treatment paradigm.
PubMed: 38796787
DOI: 10.1080/01676830.2024.2353235 -
Waste Management (New York, N.Y.) Jun 2024This study aims to investigate the microbiological working environment of biowaste workers, focusing on airborne fungal and bacterial species exposure, size...
This study aims to investigate the microbiological working environment of biowaste workers, focusing on airborne fungal and bacterial species exposure, size distribution, and species on workers' hands. The research, conducted across six plants with 45 personal exposure assessments, revealed a total of 150 bacterial species and 47 fungal species on workers' hands, including 19 and 9 species classified in risk class 2 (RC2), respectively. Workers' exposure analysis identified 172 bacterial and 32 fungal species, with several in RC2. In work areas, 55 anaerobic bacterial species belonging to RC2 were found. Different species compositions were observed in various particle size fractions, with the highest species richness for anaerobic bacteria in the fraction potentially depositing in the secondary bronchi and for fungi in the pharynx fraction. The geometric mean aerodynamic diameter (D) of RC2 anaerobic bacteria was 3.9 µm, <1.6 µm for Streptomyces, 3.4 µm for Aspergillus, and 2.0 µm for Penicillium. Overlapping species were identified on workers' hands, in their exposure, and in work areas, with Bacillus amyloliquefaciens, Leuconostoc mesenteroides, Bacillus cereus, Enterococcus casseliflavus, and Aspergillus niger consistently present. While the majority of RC2 bacterial species lacked documented associations with occupational health problems, certain bacteria and fungi, including Bacillus cereus, Escherichia coli, Enterobacter, Klebsiella pneumonia, Aspergillus fumigatus, Aspergillus niger, Aspergillus flavus, Lichtheimia corymbifera, Lichtheimia ramosa, and Paecilomyces variotii, have previously been linked to occupational health issues. In conclusion, biowaste workers were exposed to a wide range of microorganisms including RC2 species which would deposit in different parts of the airways.
Topics: Humans; Fungi; Bacteria; Occupational Exposure; Air Microbiology; Hand; Environmental Monitoring; Inhalation Exposure; Air Pollutants, Occupational
PubMed: 38788497
DOI: 10.1016/j.wasman.2024.05.018 -
Journal of Fungi (Basel, Switzerland) May 2024Invasive fungal infections have recently been recognized by the WHO as a major health, epidemiological, and economic issue. Their high mortality rates and the emergence... (Review)
Review
Invasive fungal infections have recently been recognized by the WHO as a major health, epidemiological, and economic issue. Their high mortality rates and the emergence of drug resistance have driven the development of new molecules, including olorofim, an antifungal belonging to a new family of compounds, the orotomides. A review was conducted on the PubMed database and the ClinicalTrials.gov website to summarize the microbiological profile of olorofim and its role in the treatment of filamentous fungal infections. Twenty-four articles were included from the search and divided into two groups: an "in vitro" group focusing on minimum inhibitory concentration (MIC) results for various fungi and an "in vivo" group evaluating the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and tolerability of olorofim in animal models of fungal infection and in humans. Olorofim demonstrated in vitro and in vivo activity against numerous filamentous fungi, including azole-resistant , various dermatophytes, and endemic and dimorphic fungi. in vitro results showed higher MICs for certain species and dematiaceous fungi and ; further in vivo studies are needed. Published PK-PD data in humans are limited. The results of the ongoing phase III clinical trial are eagerly awaited to evaluate olorofim's clinical impact.
PubMed: 38786700
DOI: 10.3390/jof10050345 -
Journal of Fungi (Basel, Switzerland) Apr 2024The mold employs two high-affinity uptake systems, reductive iron assimilation (RIA) and siderophore-mediated iron acquisition (SIA), for the acquisition of the...
The mold employs two high-affinity uptake systems, reductive iron assimilation (RIA) and siderophore-mediated iron acquisition (SIA), for the acquisition of the essential trace element iron. SIA has previously been shown to be crucial for virulence in mammalian hosts. Here, we show that a lack of AcuK or AcuM, transcription factors required for the activation of gluconeogenesis, decreases the production of both extra- and intracellular siderophores in . The lack of AcuM or AcuK did not affect the expression of genes involved in RIA and SIA, suggesting that these regulators do not directly regulate iron homeostasis genes, but indirectly affect siderophore production through their influence on metabolism. Consistent with this, acetate supplementation reversed the intracellular siderophore production defect of Δ and Δ. Moreover, Δ and Δ displayed a similar growth defect under iron limitation and iron sufficiency, which suggests they have a general role in carbon metabolism apart from gluconeogenesis. In agreement with a potential role of the glyoxylate cycle in adaptation to iron starvation, transcript levels of the malate synthase-encoding were found to be upregulated by iron limitation that is partially dependent on AcuK and AcuM. Together, these data demonstrate the influence of iron availability on carbon metabolism.
PubMed: 38786682
DOI: 10.3390/jof10050327 -
Journal of Fungi (Basel, Switzerland) Apr 2024Neutrophil and (alveolar) macrophage immunity is considered crucial for eliminating . Data derived from bronchoalveloar lavage (BAL) characterizing the human...
Neutrophil and (alveolar) macrophage immunity is considered crucial for eliminating . Data derived from bronchoalveloar lavage (BAL) characterizing the human immuno-pulmonary response to are non-existent. To obtain a comprehensive picture of the immune pathways involved in chronic pulmonary aspergillosis (CPA), we performed proteome analysis on AL of 9 CPA patients and 17 patients with interstitial lung disease (ILD). The dihydrorhodamine (DHR) test was also performed on BAL and blood neutrophils from CPA patients and compared to blood neutrophils from healthy controls (HCs). BAL from CPA patients primarily contained neutrophils, while ILD BAL was also characterized by a large fraction of lymphocytes; these differences likely reflecting the different immunological etiologies underlying the two disorders. BAL and blood neutrophils from CPA patients displayed the same oxidative burst capacity as HC blood neutrophils. Hence, immune evasion by involves other mechanisms than impaired neutrophil oxidative burst capacity per se. CPA BAL was enriched by proteins associated with innate immunity, as well as, more specifically, with neutrophil degranulation, Toll-like receptor 4 signaling, and neutrophil-mediated iron chelation. Our data provide the first comprehensive target organ-derived immune data on the human pulmonary immune response to .
PubMed: 38786669
DOI: 10.3390/jof10050314 -
Journal of Fungi (Basel, Switzerland) Apr 2024Pathogenic fungi are an increasing health threat due to the rise in drug resistance. The limited number of antifungals currently available and growing incidence of...
Pathogenic fungi are an increasing health threat due to the rise in drug resistance. The limited number of antifungals currently available and growing incidence of multi-drug-resistant fungi has caused rising healthcare costs and a decreased quality of life for patients with fungal infections. Nitric oxide (NO) has previously been shown to act as an antimicrobial agent, albeit with a limited understanding of the effects of the NO-release kinetics against pathogenic fungi. Herein, the antifungal effects of four nitric oxide-releasing small molecules were studied against the pathogenic fungi , , , and , to demonstrate the broad-spectrum antifungal activity of NO. A bolus dose of NO was found to eradicate fungi after 24 h, where nitric oxide donors with shorter half-lives achieved antifungal activity at lower concentrations and thus had wider selectivity indexes. Each NO donor was found to cause a severe surface destruction of fungi, and all NO donors exhibited compatibility with currently prescribed antifungals against several different fungi species.
PubMed: 38786663
DOI: 10.3390/jof10050308 -
Antibiotics (Basel, Switzerland) May 2024Simple low-cost, nontoxic, environmentally friendly plant-extract-based polymer films play an important role in their application in medicine, the food industry, and...
Simple low-cost, nontoxic, environmentally friendly plant-extract-based polymer films play an important role in their application in medicine, the food industry, and agriculture. The addition of silver nanoparticles to the composition of these films enhances their antimicrobial capabilities and makes them suitable for the treatment and prevention of infections. In this study, polymer-based gels and films (AgRonPVA) containing silver nanoparticles (AgNPs) were produced at room temperature from fresh red onion peel extract ("Ron"), silver nitrate, and polyvinyl alcohol (PVA). Silver nanoparticles were synthesized directly in a polymer matrix, which was irradiated by UV light. The presence of nanoparticles was approved by analyzing characteristic local surface plasmon resonance peaks occurring in UV-Vis absorbance spectra of irradiated experimental samples. The proof of evidence was supported by the results of XRD and EDX measurements. The diffusion-based method was applied to investigate the antimicrobial activity of several types of microbes located in the environment of the produced samples. Bacteria ATCC 29213, ATCC BAA 747, and ATCC 15442; yeasts CBS 8836 and ATCC 90028; and microscopic fungi assays BTL G-33 and BTL G-38 were used in this investigation. The greatest effect was observed on Staphylococcus aureus, Acinetobacter baumannii, and Pseudomonas aeruginosa bacteria, defining these films as potential candidates for antimicrobial applications. The antimicrobial features of the films were less effective against fungi and the weakest against yeasts.
PubMed: 38786169
DOI: 10.3390/antibiotics13050441 -
Indian Journal of Occupational and... 2024Silicosis is a progressive pneumoconiosis caused by inhalation of crystalline silica dust commonly seen in workers of construction sites, flour mills, and mining....
Silicosis is a progressive pneumoconiosis caused by inhalation of crystalline silica dust commonly seen in workers of construction sites, flour mills, and mining. Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus fumigatus antigens commonly encountered in patients with asthma and cystic fibrosis. We report a case of 60-year-old flour mill worker presented with clinico-radiological features of silicosis; further evaluation was found to have an overlap of ABPA in view of severe atopic symptoms. We describe a rare duet of silicosis with ABPA overlap.
PubMed: 38783879
DOI: 10.4103/ijoem.ijoem_170_23