SummaryInnate immunity is a semi-specific and widely distributed form of immunity, which represents the first line of defence against pathogens. This type of immunity is critical to maintain homeostasis and prevent microbe invasion, eliminating a great variety of pathogens and contributing with the activation of the adaptive immune response. The components of innate immunity include physical and chemical barriers, humoral and cell-mediated components, which are present in all jawed vertebrates. The understanding of innate defence mechanisms in non-mammalian vertebrates is the key to comprehend the general picture of vertebrate innate immunity and its evolutionary history. This is also essential for the identification of new molecules with applications in immunopharmacology and immunotherapy. In this review, we describe and discuss the main elements of vertebrate innate immunity, presenting core findings in this field and identifying areas that need further investigation.

Drug transporters play an important role in the maintenance of chemical balance and homeostasis in different tissues. In addition to their physiological functions, they are crucial for the absorption, distribution, and elimination of many clinically important drugs, thereby impacting therapeutic efficacy and toxicity. Increasing evidence has demonstrated that infectious, metabolic, inflammatory, and neurodegenerative diseases alter the expression and function of drug transporters. However, the current knowledge on transporter regulation in critical protective barriers, such as the brain and placenta, is still limited and requires more research. For instance, while many studies have examined P-glycoprotein, it is evident that research on the regulation of highly expressed transporters in the blood–brain barrier and blood–placental barrier are lacking. The aim of this review is to summarize the currently available literature in order to better understand transporter regulation in these critical barriers.

Regulated or programmed cell death plays a critical role in the development and tissue organization and function. In addition, it is intrinsically connected with immunity and host defence. An increasing cellular and molecular findings cause a change in the concept of cell death, revealing an expanding network of regulated cell death modalities and their biochemical programmes. Likewise, recent evidences demonstrate the interconnection between cell death pathways and how they are involved in different immune mechanisms. This work provides an overview of the main cell death programmes and their implication in innate immunity not only as an immunogenic/inflammatory process, but also as an active defence strategy during immune response and at the same time as a regulatory mechanism.

Non-small cell lung cancer constitutes one the most frequent and lethal forms of the disease. The antitumor peptide CIGB-552 is a new targeted anticancer therapy which molecular mechanism is associated with the inhibition of the transcription factor NF-kB, mediated by COMMD1 protein stabilization. However, its pharmacological potential in combination with chemotherapy is unknown. In this study, we examined the antiproliferative capacity of CIGB-552 in combination with chemotherapeutic agents in the non-small cell lung cancer cell line NCI-H460 and we con rmed drug interactions in vivo, in a mouse model of TC-1 lung cancer. We focus our research in the combination of CIGB-552 and the antineoplastic agent Cisplatin (CDDP) in a concomitant treatment. Our results demonstrate a clear synergic effect between 37.5 µM of CIGB-552 and 5 µM of CDDP under concomitant scheme, on proliferation inhibition, cell cycle arrest, apoptosis induction and oxidative stress response. The effect of CIGB-552 (1 mg/kg) and CDDP (0.4 mg/kg) administrated as a combined therapy was demonstrated in vivo in the TC-1 murine model where the combination achieved an effective antitumor response, without any deterioration signs or side effects. These ndings demonstrate the e cacy of the concomitant combination of both drugs in preclinical studies and support the use of this therapy in clinical trials.

Non-small cell lung cancer constitutes one the most frequent and lethal forms of the disease. The antitumor peptide CIGB-552 is a new targeted anticancer therapy which molecular mechanism is associated with the inhibition of the transcription factor NF-kB, mediated by COMMD1 protein stabilization. However, its pharmacological potential in combination with chemotherapy is unknown. In this study, we examined the antiproliferative capacity of CIGB-552 in combination with chemotherapeutic agents in the non-small cell lung cancer cell line NCI-H460 and we confirmed drug interactions in vivo, in a mouse model of TC-1 lung cancer. We focus our research in the combination of CIGB-552 and the antineoplastic agent Cisplatin (CDDP) in a concomitant treatment. Our results demonstrate a clear synergic effect between 37.5 µM of CIGB-552 and 5 µM of CDDP under concomitant scheme, on proliferation inhibition, cell cycle arrest, apoptosis induction and oxidative stress response. The effect of CIGB-552 (1 mg/kg) and CDDP (0.4 mg/kg) administrated as a combined therapy was demonstrated in vivo in the TC-1 murine model where the combination achieved an effective antitumor response, without any deterioration signs or side effects. These findings demonstrate the efficacy of the concomitant combination of both drugs in preclinical studies and support the use of this therapy in clinical trials.