Paracoccidioidomycosis presents a variety of clinical manifestations and Paracoccidioides brasiliensis can reach many tissues, most importantly the lungs. The ability of the pathogen to interact with host surface structures is essential to its virulence. The interaction between P. brasiliensis and epithelial cells has been studied, with particular emphasis on the induction of apoptosis. To investigate the expression of different apoptosis-inducing pathways in human A549 cells, we infected these cells with P. brasiliensis Pb18SP (subcultured) and 18R (recently isolated from cell culture and showing a high adhesion pattern) samples in vitro. The expressions of Bcl-2, Bak and caspase 3 were analysed by flow cytometry and DNA fragmentation using the TUNEL technique. Apoptosis of human A549 cells was induced by P. brasiliensis in a sample and time-dependent manner. Using an in vitro model, our data demonstrates that caspase 3, Bak, Bcl-2 and DNA fragmentation mediate P. brasiliensis-induced apoptosis in A549 cells. The overall mechanism is a complex process, which may involve several signal transduction pathways. These findings could partially explain the efficient behaviour of this fungus in promoting tissue infection and/or blood dissemination.
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http://dx.doi.org/10.1590/s0074-02762009000500015 | DOI Listing |
BMC Microbiol
January 2025
Department of Medical Microbiology and Immunology, Faculty of Medicine, Benha University, Benha, Egypt.
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J Cancer Res Clin Oncol
January 2025
School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Rapamycin, a macrocyclic antibiotic derived from the actinomycetes Streptomyces hygroscopicus, is a widely used immunosuppressant and anticancer drug. Even though rapamycin is regarded as a multipotent drug acting against a broad array of anomalies and diseases, the mechanism of action of rapamycin and associated pathways have not been studied and reported clearly. Also reports on the binding of rapamycin to cancer cell receptors are limited to the serine/threonine protein kinase mTORC1.
View Article and Find Full Text PDFBiochem Pharmacol
January 2025
CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China. Electronic address:
CAR-T cell therapy has been proven to be effective on hematological tumors, although graft-versus-host disease and cytokine release syndrome(CRS) limit its application to a certain extent. However, CAR-T therapy for solid tumors met challenges, among which the lack of tumor-specific antigens (TSA) and immunosuppressive tumor microenvironment (TME) are the most important factors. CAR-NK could be a good alternative to CAR-T in some ways since they can induce mild CRS and are independent of HLA-matching, but the efficacy of CAR-NKs remains limited in solid tumors.
View Article and Find Full Text PDFPLoS Negl Trop Dis
January 2025
Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Hemolysin co-regulated protein 1 (Hcp1) is a component of the cluster 1 Type VI secretion system (T6SS1) that plays a key role during the intracellular lifecycle of Burkholderia pseudomallei. Hcp1 is recognized as a promising target antigen for developing melioidosis diagnostics and vaccines. While the gene encoding Hcp1 is retained across B.
View Article and Find Full Text PDFInt J Health Sci (Qassim)
January 2025
Department of Pharmaceutical Sciences, College of Pharmacy, Umm Al Qura University, Makkah, Saudi Arabia.
Objective: Dasatinib (DTB) is a second-generation tyrosine kinase inhibitor that was found it could help with lung cancer treatment. However, DTB has low aqueous solubility and poor bioavailability due to its incomplete absorption and high first-pass effect. The objective of this study was to improve DTB's solubility, delivery, and efficacy as a potential lung cancer treatment by developing an inhalable DTB-nanoemulsion (DNE) formulation.
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