Figure - available from: Frontiers in Oncology
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Topology of somatic hypermutation in IgA versus IgG multiple myeloma. Ratio of replacement to silent mutations (R:S) in the VH FRs and VH CDRs in cases expressing the 4 commonly frequent IGHV genes of MM patients with IgG and IgA isotypes: IGHV3-23 (A), IGHV3-30 (B), IGHV4-59 (C) and IGHV3-9 (D). Asterisks indicate the statistically significant differences between the VH FR and VH CDR regions (p-value ≤ 0.05(*), p-value ≤ 0.01 (**) and p-value ≤ 0.001 (***)).
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The analysis of the immunogenetic background of multiple myeloma (MM) has proven key to understanding disease ontogeny. However, limited information is available regarding the immunoglobulin (IG) gene repertoire in MM cases carrying different heavy chain isotypes. Here, we studied the IG gene repertoire in a series of 523 MM patients, of whom 165 a...
Citations
... IgA serves as a primary defense antibody on the mucosal surface of the intestines, safeguarding the delicate intestinal lining through the neutralization of potential pathogens or harmful bacteria (Bohländer et al., 2021). lgG is the main immunoglobulin in serum and body fluids, which can enhance immune cells to phagocytose pathogenic microorganisms and fight infection (Gkoliou G et al., 2023). As shown in Figure 7, the RJP-Cu-H led to significantly higher IgA and IgG secretion compared to the control group (p < 0.05). ...
Background: Polysaccharide metal chelate exhibit both immunoregulatory activity and metal element supplementation effects.
Methods: In this study, Ruoqiang jujube polysaccharide copper chelate (RJP-Cu) was prepared and the preparation conditions were optimized using the response surface method. Subsequently, RJP-Cu was administered to lambs to evaluate its impact on growth performance, copper ion (Cu ²⁺ ) supplementation, immune enhancement, and intestinal flora was evaluated.
Results: The results indicated that optimal RJP-Cu chelation conditions included a sodium citrate content of 0.5 g, a reaction temperature of 50°C, and a solution pH of 8.0, resulting in a Cu ²⁺ concentration of 583°mg/kg in RJP-Cu. Scanning electron microscopy (SEM) revealed significant structural changes in RJP before and after chelation. RJP-Cu displaying characteristic peaks of both polysaccharides and Cu ²⁺ chelates. Blood routine indexes showed no significant differences among the RJP-Cu-High dose group (RJP-Cu-H), RJP-Cu-Medium dose group (RJP-Cu-M), RJP-Cu-low dose group (RJP-Cu-L) and the control group ( p > 0.05). However, compared with the control group, the RJP-Cu-H, M, and L dose groups significantly enhanced lamb production performance ( p < 0.05). Furthermore, RJP-Cu-H, M, and L dose groups significantly increased serum Cu ²⁺ concentration, total antioxidant capacity (T-AOC), catalase (CAT), and total superoxide dismutase (T-SOD) contents compared with control group ( p < 0.05). The RJP-Cu-H group exhibited significant increases in serum IgA and IgG antibodies, as well as the secretion of cytokines IL-2, IL-4, and TNF-α compared to the control group (p < 0.05). Furthermore, RJP-Cu-H group increased the species abundance of lamb intestinal microbiota, abundance and quantity of beneficial bacteria, and decrease the abundance and quantity of harmful bacteria. The RJP-Cu-H led to the promotion of the synthesis of various Short Chain Fatty Acids (SCFAs), improvements in atrazine degradation and clavulanic acid biosynthesis in lambs, while reducing cell apoptosis and lipopolysaccharide biosynthesis.
Conclusion: Thus, these findings demonstrate that RJP-Cu, as a metal chelate, could effectively promote lamb growth performance, increase Cu ²⁺ content, and potentially induce positive immunomodulatory effects by regulating antioxidant enzymes, antibodies, cytokines, intestinal flora, and related metabolic pathways.
... MM is the second most common type of hematological malignancy worldwide, which accounts for approximately 10% of cases [2] . The mean age of diagnosis is 69 years, and the disease diagnosis is based on the monoclonal M protein produced by malignant B cells [3] . Myeloma cells are plasma cells that secrete immunoglobulins and usually synthesize IgG or IgA [4] . ...
Multiple myeloma (MM) is a type of hematological cancer that occurs when B cells become malignant. Various drugs such as proteasome inhibitors, immunomodulators, and compounds that cause DNA damage can be used in the treatment of MM. Autophagy, a type 2 cell death mechanism, plays a crucial role in determining the fate of B cells, either promoting their survival or inducing cell death. Therefore, autophagy can either facilitate the progression or hinder the treatment of MM disease. In this review, autophagy mechanisms that may be effective in MM cells were covered and evaluated within the contexts of unfolded protein response (UPR), bone marrow microenvironment (BMME), drug resistance, hypoxia, DNA repair and transcriptional regulation, and apoptosis. The genes that are effective in each mechanism and research efforts on this subject were discussed in detail. Signaling pathways targeted by new drugs to benefit from autophagy in MM disease were covered. The efficacy of drugs that regulate autophagy in MM was examined, and clinical trials on this subject were included. Consequently, among the autophagy mechanisms that are effective in MM, the most suitable ones to be used in the treatment were expressed. The importance of 3D models and microfluidic systems for the discovery of new drugs for autophagy and personalized treatment was emphasized. Ultimately, this review aims to provide a comprehensive overview of MM disease, encompassing autophagy mechanisms, drugs, clinical studies, and further studies.
... Some myelomas may also evade apoptosis by uncontrolled transcription of BCL-2 protein, facilitated by gene deletions or the amplification of the miR-17-92 cluster. In approximately 87% of IgG cases, the BCL-2 gene is found to be translocated downstream of the gene encoding the immunoglobulin heavy chain, leading to its overexpression (Bazarbachi et al., 2021;MAATAOUI et al., 2021;Wang et al., 2021;Gkoliou et al., 2023). About 35% of patients with MM exhibit BCL-2 overexpression, which is associated with a poor prognosis. ...
Abnormal cellular apoptosis plays a pivotal role in the pathogenesis of Multiple Myeloma (MM). Over the years, BCL-2, a crucial anti-apoptotic protein, has garnered significant attention in MM therapeutic research. Venetoclax (VTC), a small-molecule targeted agent, effectively inhibits BCL-2, promoting the programmed death of cancerous cells. While VTC has been employed to treat various hematological malignancies, its particular efficacy in MM has showcased its potential for broader clinical applications. In this review, we delve into the intricacies of how VTC modulates apoptosis in MM cells by targeting BCL-2 and the overarching influence of the BCL-2 protein family in MM apoptosis regulation. Our findings highlight the nuanced interplay between VTC, BCL-2, and MM, offering insights that may pave the way for optimizing therapeutic strategies. Through this comprehensive analysis, we aim to lay a solid groundwork for future explorations into VTC’s clinical applications and the profound effects of BCL-2 on cellular apoptosis.
