Role of targeting ferroptosis as a component of combination therapy in combating drug resistance in colorectal cancer

Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.

Effect of Allocryptopine on Late sodium current of atrial myocytes in spontaneously hypertensive rats

Objective To explore the effect of allocryptopine （All） on the Late sodium current （INa,Late） of atrial myocytes in spontaneously hyper- tensive rats （SHR）. Method The enzyme digestion method was used to separate single atrial myocytes from SHR and Wistar-Kyoto rat （WKY） rats. INa,Late was record by patch-clamp technique and the effect of All on the current was evaluated. Results Comparing with WKY cells, markedly increasing of INa,Late current in SHR myocytes was found from 0.24 ± 0.02 pA/pF of WKY cells to 1.73± 0.04 pA/pF of SHR cells （P 〈 0.01, n = 15）. After treament with 30 μmol/L All; the current densities was reduced to 0.92 ± 0.03 pA/pF. The ratio of INa,Late/INa,peak of WKY and SHR were 0.09% ± 0.01% and 0.71% ± 0.02%, INa, Late/INa,peak of SHR was reduced to 0.37% ± 0.02% by 30 μmol/L All （P 〈 0.01, n = 15）. We also determined the effect of All on the gating mechanism of the INa,Late in the SHR cells. It was found that All decreased the INa,Late by alleviating the inactivation of the channels and increasing the window current of sodium channel. Conclusion Increased INa,Late in SHR atrial myocytes and the prolonged APD were inhibited by All coming from Chinese herb medicine.

Within-host model of respiratory virus shedding and antibody response to H9N2 avian influenza virus vaccination and infection in chickens

Avian influenza virus(AIV)H9N2 subtype is an infectious pathogen that can affect both the respiratory and gastrointestinal systems in chickens and continues to have an important economic impact on the poultry industry.While the host innate immune response provides control of virus replication in early infection,the adaptive immune response aids to clear infections and prevent future invasion.Modelling virus-innate immune response pathways can improve our understanding of early infection dynamics and help to guide our understanding of virus shedding dynamics that could lead to reduced transmission between hosts.While some countries use vaccines for the prevention of H9N2 AIV in poultry,the virus continues to be endemic in regions of Eurasia and Africa,indicating a need for improved vaccine efficacy or vaccination strategies.Here we explored how three type-I interferon(IFN)pathways affect respiratory virus shedding patterns in infected chickens using a within-host model.Additionally,prime and boost vaccination strategies for a candidate H9N2 AIV vaccine are assessed for the ability to elicit seroprotective antibody titres.The model demonstrates that inclusion of virus sensitivity to intracellular type-I IFN pathways results in a shedding pattern most consistent with virus titres observed in infected chickens,and the inclusion of a cellular latent period does not improve model fit.Furthermore,early administration of a booster dose two weeks after the initial vaccine is administered results in seroprotective titres for the greatest length of time for both broilers and layers.These results demonstrate that type-I IFN intracellular mechanisms are required in a model of respiratory virus shedding in H9N2 AIV infected chickens,and also highlights the need for improved vaccination strategies for laying hens.