A comprehensive perspective on the interaction between gut microbiota and COVID-19 vaccines.

The efficacy of COVID-19 vaccines varies between individuals and populations, and the reasons for this are still not fully understood. Recent clinical studies and animal models have indicated that the gut microbiota may influence the immunogenicity of the vaccine and, thus, its effectiveness. This suggests that there is a bidirectional relationship between the gut microbiota and the COVID-19 vaccine, with the varying components of the microbiota either enhancing or reducing the vaccine's efficacy. To put an end to the spread of the COVID-19 pandemic, the necessity of vaccines that create powerful and long-term immunity is now more important than ever, and understanding the role of the gut microbiota in this process is essential. Conversely, COVID-19 vaccines also have a significant effect on the gut microbiota, decreasing its total number of organisms and the variety of species present. In this Review, we analyze the evidence that suggesting an interaction between the gut microbiota and COVID-19 vaccine effectiveness, consider the immunological mechanisms that may be responsible for this connection, and explore the possibility of using gut microbiota-focused interventions to improve the efficacy of COVID-19 vaccines.

Co-inhibition of pol θ and HR genes efficiently synergize with cisplatin to suppress cisplatin-resistant lung cancer cells survival.

Cisplatin exert its anticancer effect by creating intrastrand and interstrand DNA cross-links which block DNA replication and is a major drug used to treat lung cancer. However, the main obstacle of the efficacy of treatment is drug resistance. Here, we show that expression of translesion synthesis (TLS) polymerase Q (POLQ) was significantly elevated by exposure of lung cancer cells A549/DR (a cisplatin-resistant A549 cell line) to cisplatin. POLQ expression correlated inversely with homologous recombination (HR) activity. Co-depletion of BRCA2 and POLQ by siRNA markedly increased sensitivity of A549/DR cells to cisplatin, which was accompanied with impairment of double strand breaks (DSBs) repair reflected by prominent cell cycle checkpoint response, increased chromosomal aberrations and persistent colocalization of p-ATM and 53BP1 foci induced by cisplatin. Thus, co-knockdown of POLQ and HR can efficiently synergize with cisplatin to inhibit A549/DR cell survival by inhibiting DNA DSBs repair. Similar results were observed in A549/DR cells co-depleted of BRCA2 and POLQ following BMN673 (a PARP inhibitor) treatment. Importantly, the sensitization effects to cisplatin and BMN673 in A549/DR cells by co-depleting BRCA2 and POLQ was stronger than those by co-depleting BRCA2 and other TLS factors including POLH, REV3, or REV1. Our results indicate that there is a synthetic lethal relationship between pol θ-mediated DNA repair and HR pathways. Pol θ may be considered as a novel target for lung cancer therapy.