Racial/Ethnic Disparities and Immunotherapeutic Advances in the Treatment of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) remains one of the leading causes of death among many associated liver diseases. Various conventional strategies have been utilized for treatment, ranging from invasive surgeries and liver transplants to radiation therapy, but fail due to advanced disease progression, late screening/staging, and the various etiologies of HCC. This is especially evident within racially distinct populations, where incidence rates are higher and treatment outcomes are worse for racial/ethnic minorities than their Caucasian counterparts. However, with the rapid development of genetic engineering and molecular and synthetic biology, many novel strategies have presented promising results and have provided potential treatment options. In this review, we summarize past treatments, how they have shaped current treatments, and potential treatment strategies for HCC that may prove more effective in the future.

Rescue of pyrimidine-defective Pseudomonas aeruginosa through metabolic complementation.

Chronic infections harbor multiple pathogens where dynamic interactions between members of the polymicrobial community play a major role in determining the infection outcome. For example, in a nutrient-rich polymicrobial infection, bacteria have the potential to undergo evolutionary changes that impair their ability to synthesize essential metabolites. This adaptation may facilitate metabolic interdependencies between neighboring pathogens and lead to difficult-to-treat chronic infections. Our research group previously demonstrated that Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA), typically considered classical competitors, can adopt a cooperative lifestyle through bi-directional purine exchange medicated by exogenous DNA (eDNA) release. To further validate our initial findings, in this study, we investigated the potential exchange of pyrimidine between PA and other pathogens, which is another constituent of DNA. In our findings, we observed that a pyrimidine-deficient transposon mutant strain of PA showed improved growth when co-cultured with wild-type PA, SA, Acinetobacter baumannii (AB), and Enterococcus faecalis (EF). Additionally, improved fitness of pyrimidine-deficient PA was further observed in chemical complementation with eDNA and uridine-5'-monophosphate. Interestingly, the rescue of PA growth through eDNA complementation is not as effective as in intact cells, such as SA, AB, EF, and wild-type PA, implying that eDNA is a lesser contributor to this metabolic complementation. Also, the exchange mechanism between pathogens involves more active mechanisms beyond simple eDNA or metabolite release. Our data further highlights the importance of cell-to-cell contact for effective and increased metabolic complementation. IMPORTANCE: This research holds crucial implications for combating chronic infections, where multiple pathogens coexist and interact within the same environment. By uncovering the dynamic exchange of pyrimidines between Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA), our study reveals a previously unrecognized aspect of interspecies cooperation. The observed enhanced growth of a pyrimidine-deficient PA strain when co-cultured with SA suggests potential avenues for understanding and disrupting bacterial metabolic interdependencies in chronic infection settings. Furthermore, our findings highlight the mechanisms involved in metabolic exchange, emphasizing the importance of cell-to-cell contact. This research explored essential metabolic interactions to address the challenges posed by difficult-to-treat chronic infections.