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Marine Drugs Jun 2024Four new cyclic pentapeptides, avellanins D-G (-), together with four known compounds (-), were isolated from a mangrove-derived GXIMD 03099 fungus from L. Their...
Four new cyclic pentapeptides, avellanins D-G (-), together with four known compounds (-), were isolated from a mangrove-derived GXIMD 03099 fungus from L. Their structures were elucidated by analysis of HRESIMS, NMR, and ESI-MS/MS data. Their absolute configurations were determined by X-ray diffraction analysis and Marfey's method. Compounds - were screened for insecticidal and antibacterial activities. Compound showed insecticidal activity against newly hatched larvae of with an LC value of 86.6 µM; compound had weak activity against with an MIC value of 5.85 µM.
Topics: Aspergillus fumigatus; Peptides, Cyclic; Animals; Anti-Bacterial Agents; Insecticides; Microbial Sensitivity Tests; Vibrio; Culex; Larva; Molecular Structure
PubMed: 38921593
DOI: 10.3390/md22060282 -
Marine Drugs Jun 2024Cyclic pentapeptide compounds have garnered much attention as a drug discovery resource. This study focused on the characterization and anti-benign prostatic hyperplasia...
Cyclic pentapeptide compounds have garnered much attention as a drug discovery resource. This study focused on the characterization and anti-benign prostatic hyperplasia (BPH) properties of avellanin A from fungus in marine sediment samples collected in the Beibu Gulf of Guangxi Province in China. The antiproliferative effect and molecular mechanism of avellanin A were explored in testosterone propionate (TP)-induced RWPE-1 cells. The transcriptome results showed that avellanin A significantly blocked the ECM-receptor interaction and suppressed the downstream PI3K-Akt signalling pathway. Molecular docking revealed that avellanin A has a good affinity for the cathepsin L protein, which is involved in the terminal degradation of extracellular matrix components. Subsequently, qRT-PCR analysis revealed that the expression of the genes , , , , , , , and was significantly downregulated after avellanin A intervention. The Western blot results also confirmed that it not only reduced ITGB3 and FAK/p-FAK protein expression but also inhibited PI3K/p-PI3K and Akt/p-Akt protein expression in the PI3K-Akt signalling pathway. Furthermore, avellanin A downregulated Cyclin D1 protein expression and upregulated Bax, p21, and p53 proapoptotic protein expression in TP-induced RWPE-1 cells, leading to cell cycle arrest and inhibition of cell proliferation. The results of this study support the use of avellanin A as a potential new drug for the treatment of BPH.
Topics: Humans; Proto-Oncogene Proteins c-akt; Signal Transduction; Cell Proliferation; Phosphatidylinositol 3-Kinases; Molecular Docking Simulation; Cell Line; Male; Apoptosis
PubMed: 38921586
DOI: 10.3390/md22060275 -
Journal of Fungi (Basel, Switzerland) May 2024The efficacy of different echinocandins is assessed by evaluating the in vitro activity of a novel antifungal, rezafungin, against invasive fungal isolates in comparison...
The efficacy of different echinocandins is assessed by evaluating the in vitro activity of a novel antifungal, rezafungin, against invasive fungal isolates in comparison with anidulafungin and caspofungin. Using the broth microdilution (BMD) method, the susceptibility of 1000 clinical isolates (including 400 , 200 , 200 , 150 and 50 ) and 150 isolates (100 and 50 ) from the Eastern China Invasive Fungi Infection Group (ECIFIG) was tested for the antifungals including anidulafungin, rezafungin, caspofungin and fluconazole. The echinocandins showed strong activity against that was maintained against fluconazole-resistant isolates. The GM MIC (geometric mean minimum inhibitory concentration) value of rezafungin was found to be comparable to that of anidulafungin or caspofungin against the five tested common species. exhibited higher resistance rates (about 8.67-40.67% in different antifungals) than the other four species. Through the sequencing of genes, we searched for mutations in echinocandin-resistant isolates and found that all displayed alterations in S654P. The determined MEC (minimal effective concentration) values against and for rezafungin (0.116 μg/mL, 0.110 μg/mL) are comparable to those of caspofungin (0.122 μg/mL, 0.142 μg/mL) but higher than for anidulafungin (0.064 μg/mL, 0.059 μg/mL). Thus, the in vitro activity of rezafungin appears comparable to anidulafungin and caspofungin against most common and species. Rezafungin showed higher susceptibility rates against . Rezafungin indicates its potent activity for potential clinical application.
PubMed: 38921383
DOI: 10.3390/jof10060397 -
Current Issues in Molecular Biology Jun 2024is commonly found in the airway and is associated with airway inflammatory diseases. Zinc oxide (ZO) is known to be an essential microelement that facilitates fungal...
is commonly found in the airway and is associated with airway inflammatory diseases. Zinc oxide (ZO) is known to be an essential microelement that facilitates fungal survival, growth, and proliferation. This study aimed to investigate the impact of ZO on -induced fungal sinusitis in rabbits. Twenty-eight New Zealand white rabbits were divided into four groups for this study. Group 1 (6 sides) was treated with intramaxillary phosphate buffer saline (PBS) served as the negative control, Group 2 (6 sides) received intramaxillary PBS and ZO, Group 3 (8 sides) was treated with intramaxillary alone, and Group 4 (8 sides) treated with intramaxillary with ZO. After 4 and 12 weeks, sinus mucosal cytokine and transcription factor expressions were determined. A histological analysis was performed to determine inflammatory cell infiltration, number of secretory cells, and mucosal thickness. Fungal biofilm formation was determined using confocal laser microscopy. The intramaxillary instillation of conidia led to an increase in protein and mRNA expression of interleukin (IL)-1β and IL-8 in the maxillary sinus mucosa. They were associated with mitogen-activated protein kinase and activator protein-1. Furthermore, intramaxillary instillation of fungal conidia resulted in significant enhancement of inflammatory cell infiltration, epithelial thickening, and fungal biofilm formation. However, intramaxillary ZO did not have a significant impact on -induced cytokine protein and mRNA expression, and inflammatory cell infiltration and epithelial thickness in sinonasal mucosa. While intramaxillary instillation of increased mucosal inflammation, cytokine production, and biofilm formation, the intramaxillary application of ZO did not have a significant influence on inflammation in the maxillary sinus mucosa.
PubMed: 38921013
DOI: 10.3390/cimb46060342 -
Open Biology Jun 2024is the predominant mould pathogen for humans. Adaption to host-imposed iron limitation has previously been demonstrated to be essential for its virulence. [2Fe-2S]...
is the predominant mould pathogen for humans. Adaption to host-imposed iron limitation has previously been demonstrated to be essential for its virulence. [2Fe-2S] clusters are crucial as cofactors of several metabolic pathways and mediate cytosolic/nuclear iron sensing in fungi including . [2Fe-2S] cluster trafficking has been shown to involve BolA family proteins in both mitochondria and the cytosol/nucleus. Interestingly, both homologues, termed Bol1 and Bol3, possess mitochondrial targeting sequences, suggesting the lack of cytosolic/nuclear versions. Here, we show by the combination of mutational, proteomic and fluorescence microscopic analyses that expression of the Bol3 encoding gene leads to dual localization of gene products to mitochondria and the cytosol/nucleus via alternative translation initiation downstream of the mitochondrial targeting sequence, which appears to be highly conserved in various species. Lack of either mitochondrial Bol1 or Bol3 was phenotypically inconspicuous while lack of cytosolic/nuclear Bol3 impaired growth during iron limitation but not iron sensing which indicates a particular importance of [2Fe-2S] cluster trafficking during iron limitation. Remarkably, cytosolic/nuclear Bol3 differs from the mitochondrial version only by N-terminal acetylation, a finding that was only possible by mutational hypothesis testing.
Topics: Aspergillus fumigatus; Fungal Proteins; Cytosol; Mitochondria; Iron; Adaptation, Physiological; Cell Nucleus; Protein Transport; Proteomics; Iron-Sulfur Proteins; Gene Expression Regulation, Fungal; Acetylation
PubMed: 38919062
DOI: 10.1098/rsob.240033 -
Annali Italiani Di Chirurgia 2024Aspergillosis is the most common invasive fungal infection among lung transplant recipients (LTRs). Although its incidence is lower than that of bacterial or viral...
AIM
Aspergillosis is the most common invasive fungal infection among lung transplant recipients (LTRs). Although its incidence is lower than that of bacterial or viral infections, it poses a similar or even higher mortality rate due to challenges in early diagnosis, limited treatment options, and various complications. Therefore, we aimed to evaluate the pulmonary aspergillosis cases in our tertiary lung transplant center.
METHODS
A retrospective analysis of 146 LTRs was performed. The demographic data, microbiological and histopathological test results, and radiological findings used for Aspergillus identification were recorded.
RESULTS
Aspergillus spp. was detected in 13 of 146 LTRs (9%), mean age 42.5 ± 14.06 years, an average of 18.9 months after lung transplantation. 3 cases (23%) had Aspergillus growth in tissue culture, and 2 (15.4%) showed fungal elements with septal hyaline fibrils in tissue pathology. Aspergillus spp Polymerase chain reaction (PCR) was positive in bronchoalveolar lavage of 8 (61.5%) cases. In addition, 4 (30.7%) cases had relevant tomography findings. The most common pathogens were A. Terreus (21%), A. Fumigatus (14%), and A. Flavus (14%). The mortality rate was 15%.
CONCLUSIONS
LTRs are at high risk of Aspergillus spp infections. Early diagnosis with microbiological, histopathological, and radiological tests, in addition to well-established prevention strategies, prophylaxis, and treatment will provide a better survival rate for patients.
Topics: Humans; Retrospective Studies; Lung Transplantation; Adult; Invasive Pulmonary Aspergillosis; Tertiary Care Centers; Male; Female; Middle Aged; Postoperative Complications
PubMed: 38918958
DOI: 10.62713/aic.3505 -
Microbiology Spectrum Jun 2024Fungal infections are a major contributor to morbidity and mortality among immunocompromised populations. Moreover, fungal disease caused by molds are difficult to treat...
Fungal infections are a major contributor to morbidity and mortality among immunocompromised populations. Moreover, fungal disease caused by molds are difficult to treat and are associated with particularly high mortality. To address the need for new mold-active antifungal drugs, we performed a high-throughput screen with , the most common pathogenic mold. We identified a novel, pyrimidine-based chemical scaffold with broad-spectrum antifungal activity including activity against several difficult-to-treat molds. A chemical genetics screen of suggested that this compound may target the endoplasmic reticulum (ER) and perturb ER function and/or homeostasis. Consistent with this model, this compound induces the unfolded protein response and inhibits secretion of collagenases. Initial cytotoxicity and pharmacokinetic studies show favorable features including limited mammalian cell toxicity and bioavailability . Together, these data support the further medicinal chemistry and pre-clinical development of this pyrimidine scaffold toward more effective treatments for life-threatening invasive mold infections.IMPORTANCEInvasive fungal diseases are life-threatening infections caused by fungi in immunocompromised individuals. Currently, there are only three major classes of antifungal drugs available to treat fungal infections; however, these options are becoming even more limited with the global emergence of antifungal drug resistance. To address the need for new antifungal therapies, we performed a screen of chemical compounds and identified a novel molecule with antifungal activity. Initial characterization of this compound shows drug-like features and broad-spectrum activity against medically important fungi. Together, our results support the continued development of this compound as a potential future therapy for these devastating fungal infections.
PubMed: 38916314
DOI: 10.1128/spectrum.01045-24 -
American Journal of Physiology. Lung... Jun 2024Chitin, a polysaccharide found in the fungal cell wall and the exoskeletons of house dust mites and cockroaches, has garnered attention as a potential immunoreactive...
Chitin, a polysaccharide found in the fungal cell wall and the exoskeletons of house dust mites and cockroaches, has garnered attention as a potential immunoreactive allergen. Mammals have evolved to express chitin-degrading chitinases (acidic mammalian chitinase/AMCase and chitotriosidase) that may modulate immune responses to chitin. We have previously reported that mice deficient in AMCase (-/-) demonstrated better lung function during allergic fungal asthma. As expected, we show that mice overexpressing AMCase (SPAM mice) had worse airway hyperreactivity (AHR) during allergic fungal asthma. We further demonstrate that chitin-positive conidia are detectable in the allergic lung during chronic exposure. Lung function in -/- and SPAM mice directly correlated with the level of chitinase activity during chronic fungal exposure (-/- mice, negligible chitinase activity, lower AHR; SPAM mice, heightened chitinase activity, higher AHR), suggesting that the breakdown of chitin promoted AHR. However, chronic exposure of normal mice to purified chitin resulted in only moderate inflammatory changes in the lung which were not sufficient to induce AHR. Moreover, despite having dramatic differences in chitinase activity, chronic exposure of -/- and SPAM mice to purified chitin likewise did not modulate AHR. Collectively, these results indicate that chronic exposure to fungal chitin alone is incapable of driving AHR. Furthermore, our data suggests that the chitinase-mediated degradation of chitin associated with conidia may facilitate unmasking and/or liberation of other fungal cell wall components that drive inflammatory responses which contribute to AHR.
PubMed: 38915287
DOI: 10.1152/ajplung.00041.2024 -
Frontiers in Cellular and Infection... 2024Invasive mold diseases of the central nervous (CNS IMD) system are exceedingly rare disorders, characterized by nonspecific clinical symptoms. This results in...
BACKGROUND
Invasive mold diseases of the central nervous (CNS IMD) system are exceedingly rare disorders, characterized by nonspecific clinical symptoms. This results in significant diagnostic challenges, often leading to delayed diagnosis and the risk of misdiagnosis for patients. Metagenomic Next-Generation Sequencing (mNGS) holds significant importance for the diagnosis of infectious diseases, especially in the rapid and accurate identification of rare and difficult-to-culture pathogens. Therefore, this study aims to explore the clinical characteristics of invasive mold disease of CNS IMD in children and assess the effectiveness of mNGS technology in diagnosing CNS IMD.
METHODS
Three pediatric patients diagnosed with Invasive mold disease brain abscess and treated in the Pediatric Intensive Care Unit (PICU) of the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2023 were selected for this study.
RESULTS
Case 1, a 6-year-old girl, was admitted to the hospital with "acute liver failure." During her hospital stay, she developed fever, irritability, and seizures. CSF mNGS testing resulted in a negative outcome. Multiple brain abscesses were drained, and was detected in pus culture and mNGS. The condition gradually improved after treatment with voriconazole combined with caspofungin. Case 2, a 3-year-old girl, was admitted with "acute B-lymphoblastic leukemia." During induction chemotherapy, she developed fever and seizures. was detected in the intracranial abscess fluid by mNGS, and the condition gradually improved after treatment with voriconazole combined with caspofungin, followed by "right-sided brain abscess drainage surgery." Case 3, a 7-year-old girl, showed lethargy, fever, and right-sided limb weakness during the pending chemotherapy period for acute B-lymphoblastic leukemia. and was detected in the cerebrospinal fluid by mNGS. The condition gradually improved after treatment with amphotericin B combined with posaconazole. After a six-month follow-up post-discharge, the three patients improved without residual neurological sequelae, and the primary diseases were in complete remission.
CONCLUSION
The clinical manifestations of CNS IMD lack specificity. Early mNGS can assist in identifying the pathogen, providing a basis for definitive diagnosis. Combined surgical treatment when necessary can help improve prognosis.
Topics: Humans; Female; High-Throughput Nucleotide Sequencing; Child; Metagenomics; Brain Abscess; Antifungal Agents; Invasive Fungal Infections; Male; Central Nervous System Fungal Infections; Child, Preschool; Aspergillus fumigatus; Caspofungin
PubMed: 38912204
DOI: 10.3389/fcimb.2024.1393242 -
Preparative Biochemistry & Biotechnology Jun 2024This research performed cellulase production by A4112 and evaluated its potential use in palm oil mill effluent (POME) hydrolysis to recover oil simultaneously with the...
Cellulase production by A4112 and the potential use of the enzyme in cooperation with surfactant to enhance floating oil recovery and methane production from palm oil mill effluent.
This research performed cellulase production by A4112 and evaluated its potential use in palm oil mill effluent (POME) hydrolysis to recover oil simultaneously with the generation of fermentable sugar useful for biofuel production under non-sterilized conditions. Empty fruit bunch (EFB) without pretreatment was used as carbon source. The combination of nitrogen sources facilitated CMCase production. The maximum activity (3.27 U/mL) was obtained by 1.0 g/L peptone and 1.5 g/L (NH)SO and 20 g/L EFB at 40 °C for 7 days. High level of FPase activity (39.51 U/mL) was also obtained. Interestingly, the enzyme retained its cellulase activities more than 60% at ambient temperature over 15 days. In enzymatic hydrolysis, Triton X-100 was an effective surfactant to increase total oil recovery in the floating form. High yield of reducing sugar (50.13 g/L) and 21% (v/v) of floating oil was recoverable at 65 °C for 48 h. Methane content of the raw POME increased from 41.49 to 64.94% by using de-oiled POME hydrolysate which was higher than using the POME hydrolysate (59.82%). The results demonstrate the feasibility of the constructed process for oil recovery coupled with a subsequent step for methane yield enhancement in biogas production process that benefits the palm oil industry.
PubMed: 38909283
DOI: 10.1080/10826068.2024.2368627