Current Protein and Peptide Science - Volume 26, Issue 9, 2025

Circular RNAs (circRNAs) have emerged as promising candidates for neoantigen vaccine development due to their unique structural stability, enhanced translational efficiency, and immunostimulatory properties. Unlike linear RNAs, circRNAs exhibit exonuclease resistance, prolonged antigen expression, and increased activation of innate immune receptors such as RIG-I and MDA5, thereby enhancing anti-tumor immune responses. Preclinical studies have demonstrated that circRNA-based vaccines encoding tumor-specific neoantigens effectively stimulate Antigen-Presenting Cells (APCs), particularly Dendritic Cells (DCs), leading to robust CD8⁺ Cytotoxic T Lymphocyte (CTL) activation. This results in increased cytokine production, T-cell proliferation, and durable anti-tumor immunity. Compared to conventional neoantigen vaccine platforms, circRNA vaccines offer distinct advantages, including higher immunogenicity, improved cytosolic delivery, and minimal risk of genomic integration. CircRNA vaccines have demonstrated efficacy in preclinical tumor models, with studies highlighting their ability to induce long-term memory T-cell responses and enhance the efficacy of immune checkpoint blockade therapies. However, challenges remain in optimizing circRNA delivery, mitigating unintended immune activation, and scaling up manufacturing processes. The translational potential of circRNA vaccines in tumor immunotherapy is significant, offering a novel and scalable approach to personalized cancer treatment. Further research and clinical validation are needed to optimize their design, improve manufacturing efficiency, and assess their efficacy in human trials. CircRNA vaccines represent a next-generation platform with the potential to revolutionize cancer immunotherapy by harnessing durable and targeted anti-tumor immune responses.

The COVID-19 outbreak, caused by the SARS-CoV-2 coronavirus, has threatened and taken many lives since the end of 2019. Given the importance of COVID-19 worldwide, since its spread, many research groups have been seeking blood markers that could help to understand the disease establishment and prognosis. Usually, those markers are proteins with a differential accumulation only during infection. Based on that, proteomic studies have played a crucial role in elucidating diseases. Mass spectrometry (MS) is a promising technique in COVID-19 studies, allowing the identification and quantification of proteins present in the plasma or serum of affected patients. It helps us to understand pathological mechanisms, predict clinical outcomes, and develop specific therapies. MS proteomics revealed biomarkers associated with infection, disease severity, and immune response. Plasma or blood serum is easy to collect and store; however, its composition and the higher concentration of proteins (e.g., albumins) shadow the identification of less abundant proteins, which usually are essential markers. So, clean-up approaches such as depletion strategies and fractionating are often required to analyze blood samples, allowing the identification of low-abundant proteins. This review will discuss many proteomic approaches to discovering new plasma biomarkers of COVID-19 employed in recently published studies. The challenges inherent to blood samples will also be discussed, such as sample preparation, data processing, and identifying reliable biomarkers.

Gastric cancer remains one of the leading cancer-related deaths worldwide. Despite the research advances, many challenges persist because the diseases are usually diagnosed at an advanced stage and have a complex treatment protocol. Conventional treatments such as chemotherapy, radiation, and surgery pose several side effects and low efficiency. The growing worldwide interest in herbal products, particularly, their bioactive ingredients, presents a promising prospect for auxiliary or alternative therapies for gastric cancer. In vivo experiments show that the given compounds increase the effectiveness and decrease the cumulative harmful impact of conventional anticancer treatments, which may have additive effects. Furthermore, clinical trials have revealed that phytoconstituents have possible anti-gastric cancer properties in humans. Nonetheless, these encouraging preclinical observations have not progressed into clinical practice all that much due to the absence of adequately powered Phase III trials for GC. Therefore, this review stresses the need for well-controlled human interventions to confirm the effectiveness and safety of herb-based therapies. In the long run, the incorporation of these herbal products could present a new approach to constructing the gastric cancer prevention and treatment outlook while minimizing the side effects of conventional treatments and opening up arenas of functional foods and pharmaceuticals.

Recently, a new type of cow’s milk has been commercialized in the markets, called A2 milk. It is derived from a specific allelic composition on chromosome 6. The only difference between A1 and A2 milk results from the polymorphism at the 67 amino acid chain. In this position, A2 milk has a proline amino acid, while A1 milk has a histidine amino acid. Proteins are one of the most important components of milk, especially casein, and have received significant attention as they are the source of bioactive opioid peptides called beta-casomorphin-7. Peptides are released through enzymatic digestion of casein and whey proteins. More precisely, this bioactive peptide is produced by sequential gastrointestinal digestion of bovine A1 variants proteins, while this phenomenon is not present in variant A2. Studies have reported that A1 milk can be harmful to health not only for adults but also for infants and that β-casein A2 becomes a safer choice following the relationship between disease risk and consumption of the beta-casomorphin-7 peptide. Indeed, epidemiological studies suggest that the released beta-casomorphin-7 peptide is a risk factor for the development of diseases in humans, but this has not yet been validated by other studies. In contrast, A2 milk has been suggested as an appropriate substitute for A1 milk since populations consuming milk containing high levels of the A2 beta-casein variant have lower rates of diseases, such as diabetes, coronary heart disease, autism, and schizophrenia.