Antimicrobial resistance (AMR) is one of the greatest global health challenges of modern times and its prevalence is rising worldwide. AMR within bacteria reduces the efficacy of antibiotics and increases both the morbidity and the mortality associated with bacterial infections. Despite this growing risk, few antibiotics with a novel mode of action are being produced, leading to a lack of antibiotics that can effectively treat bacterial infections with AMR. Metals have a history of antibacterial use but upon the discovery of antibiotics, often became overlooked as antibacterial agents. Meanwhile, metal-based complexes have been used as treatments for other diseases, such as the gold-containing drug auranofin, used to treat rheumatoid arthritis. Metal-based antibacterial compounds have novel modes of action that provide an advantage for the treatment of bacterial infections with resistance to conventional antibiotics. In this review, the antibacterial activity, mode of action, and potential for systemic use of a number of metal-based antibacterial complexes are discussed. The current limitations of these compounds are highlighted to determine if metal-based agents are a potential solution for the treatment of bacterial infections, especially those resistant to conventional antibiotics.
Human papillomaviruses (HPVs) are the etiological agent of a significant, and increasing, fraction of head and neck squamous cell carcinomas (HNSCC)-a heterogenous group of malignancies in the head and neck region. HPV infection accounts for approximately 25% of all cases, with the remainder typically caused by smoking and excessive alcohol consumption. These distinct etiologies lead to profound clinical and immunological differences between HPVpositive (HPV + ) and HPV-negative (HPV À ) HNSCC, likely related to the expression of exogenous viral antigens in the HPV + subtype. Specifically, HPV + HNSCC patients generally exhibit better treatment response compared to those with HPV À disease, leading to a more favorable prognosis, with lower recurrence rate, and longer overall survival time. Importantly, a plethora of studies have illustrated that the tumor immune microenvironment (TIME) of HPV + HNSCC has a strikingly distinct immune composition to that of its HPV À counterpart. The HPV + TIME is characterized as being immunologically "hot," with more immune infiltration, higher levels of T-cell activation, and higher levels of immunoregulation compared to the more immunologically "cold" HPV À TIME. In general, cancers with an immune "hot" TIME exhibit better treatment response and superior clinical outcomes in comparison to their immune "cold" counterparts. Indeed, this phenomenon has also been observed in HPV + HNSCC patients, highlighting the critical role of the TIME in influencing prognosis, and further validating the use of cancer therapies that capitalize on the mobilization and/or modulation of the TIME.
Although infection with human papillomavirus (HPV) is associated with nearly all cervical cancers (CC), a small proportion are HPV-negative. Recently, it has become clear that HPV-negative CC represent a distinct disease phenotype compared to HPV-positive disease and exhibit increased mortality. In addition, variations between different HPV types associated with CC have been linked to altered molecular pathology and prognosis. We compared the immune microenvironments of CC caused by HPV α9 species (HPV16-like), HPV α7 species (HPV18-like) and HPV-negative disease. HPV-negative CC appeared distinct from other subtypes, with greatly reduced levels of lymphocyte infiltration compared to either HPV α9 or α7 CC. Besides reduced levels of markers indicative of B, T, and NK lymphocytes, the expression of T-cell effector molecules, activation/exhaustion markers, and T-cell receptor diversity were also significantly lower in HPV-negative CC. Interestingly, HPV-negative CC expressed much higher levels of potential neoantigens than HPV-positive CC. These results identify profound differences between the immune landscape of HPV-positive and HPV-negative CC as well as modest differences between HPV α9 and α7 CC. These differences may contribute to altered patient outcomes between HPV-negative and HPV-positive CC and potentially between CC associated with different HPV types.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.