Synthetic glucocorticoid dexamethasone is the first trial-proven drug that reduces COVID-19 mortality by suppressing immune system. In contrast, interferons are a crucial component of host antiviral immunity and can be directly suppressed by glucocorticoids. To investigate whether therapeutic interferons can compensate glucocorticoids-induced loss of antiviral immunity, we retrospectively analyzed a cohort of 387 PCR-confirmed COVID-19 patients with quasi-random exposure to interferons and conditional exposure to glucocorticoids. Among patients receiving glucocorticoids, early interferon therapy was associated with earlier hospital discharge (adjusted HR 1.68, 95% CI 1.19-2.37) and symptom relief (adjusted HR 1.48, 95% CI 1.06-2.08), while these associations were insignificant among glucocorticoids nonusers. Early interferon therapy was also associated with lower prevalence of prolonged viral shedding (adjusted OR 0.24, 95% CI 0.10-0.57) only among glucocorticoids users. Additionally, these associations were glucocorticoid cumulative dose- and timing-dependent. These findings reveal potential therapeutic synergy between interferons and glucocorticoids in COVID-19 that warrants further investigation.
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http://dx.doi.org/10.1038/s41392-021-00496-5 | DOI Listing |
Theranostics
January 2025
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin 300353, People's Republic of China.
Hepatic carcinoma, one of the most malignant cancers in the world, has limited success with immunotherapy and a poor prognosis in patients. While pyroptosis is considered as a promising immunotherapy strategy for tumors, it still suffers from a lack of effective inducers. We designed, synthesized and screened an indole analogue, , featuring a 2, 4-thiazolidinedione substituted indole scaffold.
View Article and Find Full Text PDFNarra J
December 2024
Department of Urology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.
Prostate cancer represents the predominant malignant neoplasm observed in the male population and ranks second in terms of mortality attributable to malignant neoplasm among men. Decursinol angelate (DA), derived from the plant Nakai (AGN), has demonstrated anti-cancer effectiveness through the induction of intrinsic and extrinsic apoptosis pathways, inhibition of cancer cell proliferation, having anti- neovascularization, anti-inflammatory anti-oxidative activities and stimulating the immune process. The aim of this study was to determine the IC50 dose of DA on human prostate cancer cell line PC-3, as well as to assess its effects on cell viability and apoptosis.
View Article and Find Full Text PDFNat Commun
January 2025
Carisma Therapeutics Inc, Philadelphia, PA, USA.
We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we develop clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduce tumor burden, prolong survival, remodel the TME, increase intratumoral T cell and natural killer (NK) cell infiltration, and induce antigen spreading.
View Article and Find Full Text PDFBioinformatics
January 2025
School of Data Science and Society, University of North Carolina at Chapel Hill, NC 27599, United States.
Motivation: Forecasting the synergistic effects of drug combinations facilitates drug discovery and development, especially regarding cancer therapeutics. While numerous computational methods have emerged, most of them fall short in fully modeling the relationships among clinical entities including drugs, cell lines, and diseases, which hampers their ability to generalize to drug combinations involving unseen drugs. These relationships are complex and multidimensional, requiring sophisticated modeling to capture nuanced interplay that can significantly influence therapeutic efficacy.
View Article and Find Full Text PDFBraz J Microbiol
January 2025
Department of Postgraduate Program in Animal Science, University of Franca (UNIFRAN), Av. Dr. Armando Salles Oliveira, 201, Parque Universitário, Franca, SP, CEP 14.404-600, Brazil.
Failures in endodontic treatments are common due to microbial resistance in the pulp canal. The study evaluated the in vitro activity of polyhexamethylene guanidine hydrochloride (PHMGH) against endodontic strains, as well as in vivo toxicity. Using minimum inhibitory concentration and minimum bactericidal concentration techniques, PHMGH was effective against all microorganisms, even at low concentrations.
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