Neoplastic transformation of B cells of the post-germinative center can lead to oncohematological dyscrasias which often results in an abnormal production of monoclonal immunoglobulin light chains. The non-physiological production of large amounts of IgG light chains leads to the formation of extracellular deposits called 'aggregomas' and rare conditions such as light chain crystal deposition disease. Kidney manifestations and heavy-chain deposition disease can also occur in plasma cell dyscrasias emphasizing the role of IgG misfolding and aggregation. This minireview describes molecular mechanisms of IgG light-chain aggregation as well as the consequences and therapeutic implications of IgG light chain misfolding in these disorders. By elucidating the mechanisms of IgG light chain misfolding and aggregation researchers can identify specific molecular and cellular pathways. This knowledge opens the door to novel therapeutic targets offering the potential for interventions that can either prevent the initial misfolding events promote the proper folding and processing of immunoglobulins or enhance the clearance of misfolded proteins and aggregates. These protein folding-related issues persist even after the successful elimination of the malignant B cells. Such targeted protein-folding therapies could significantly improve patients' quality of life and contribute to their recovery. Thus a deep understanding of IgG light chain misfolding and its consequences not only sheds light on the complex biology of oncohematological dyscrasias but also opens the way for innovative treatment strategies that could transform patient care in these conditions instilling hope and motivation in the healthcare professionals and researchers in this field.

The misfolding and aggregation of amyloid proteins are closely associated with a range of neurodegenerative diseases. Liquid-liquid phase separation (LLPS) can initiate the aggregation of proteins indicating that LLPS may serve as an alternative pathway for the pathological aggregation of amyloid proteins. The co-occurrence of two or more amyloid pathologies has been observed in extensive pathophysiological studies and is linked to faster disease progression. The co-LLPS (also known as co-condensation) and co-aggregation of different disease-related proteins have been proposed as a potential molecular mechanism for combined neuropathology. Here we reviewed the current state of knowledge regarding the co-aggregation and co-condensation of various amyloid proteins including Aβ tau α-synuclein TDP-43 FUS and hnRNPA/B protein family C9orf72 dipeptide repeats and prion protein. We briefly introduced the epidemiological correlation among different neurodegenerative diseases and specifically presented recent experimental findings about co-aggregation and co-condensation of two different amyloid proteins. Additionally we discussed computational studies focusing on the molecular interactions between amyloid proteins to offer mechanistic insights into the co-LLPS and co-aggregation processes. This review provides an overview of the synergistic interactions between different disease-related proteins which is helpful for understanding the mechanisms of combined neuropathology and developing targeted therapeutic strategies.

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.

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.