Lactate dehydrogenase A is implicated in the pathogenesis of B-cell lymphoma through regulation of the FER signaling pathway.

Lactate dehydrogenase A (LDHA) is highly expressed in various tumors. However, the role of LDHA in the pathogenesis of B-cell lymphoma remains unclear. Analysis of data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases revealed an elevated LDHA expression in diffuse large B-cell lymphoma (DLBC) tissues compared with normal tissues. Similarly, our results demonstrated a significant increase in LDHA expression in tumor tissues from the patients with B-cell lymphoma compared with those with lymphadenitis. To further elucidate potential roles of LDHA in B-cell lymphoma pathogenesis, we silenced LDHA in the Raji cells (a B-cell lymphoma cell line) using shRNA techniques. Silencing LDHA led to reduced mitochondrial membrane integrity, adenosine triphosphate (ATP) production, glycolytic activity, cell viability and invasion. Notably, LDHA knockdown substantially suppressed in vivo growth of Raji cells and extended survival in mice bearing lymphoma (Raji cells). Moreover, proteomic analysis identified feline sarcoma-related protein (FER) as a differential protein positively associated with LDHA expression. Treatment with E260, a FER inhibitor, significantly reduced the metabolism, proliferation and invasion of Raji cells. In summary, our findings highlight that LDHA plays multiple roles in B-cell lymphoma pathogenesis via FER pathways, establishing LDHA/FER may as a potential therapeutic target.

Initial IL-10 production dominates the therapy of mesenchymal stem cell scaffold in spinal cord injury.

Rationale: Spinal cord injury (SCI) is an acute damage to the central nervous system that results in severe morbidity and permanent disability. Locally implanted scaffold systems with immobilized mesenchymal stem cells (MSCs) have been widely proven to promote locomotor function recovery in SCI rats; however, the underlying mechanism remains elusive. Methods and Results: In this study, we constructed a hyaluronic acid scaffold system (HA-MSC) to accelerate the adhesive growth of human MSCs and prolong their survival time in SCI rat lesions. MSCs regulate local immune responses by upregulating the expression of anti-inflammatory cytokines. Interestingly, the dramatically increased, but transient expression of interleukin 10 (IL-10) is found to be secreted by MSCs in the first week. Blocking the function of the initially produced IL-10 by the antibody completely abolished the neurological and behavioral recovery of SCI rats, indicating a core role of IL-10 in SCI therapy with HA-MSC implantation. Transcriptome analyses indicated that IL-10 selectively promotes the migration and cytokine secretion-associated programs of MSCs, which in turn helps MSCs exert their anti-inflammatory therapeutic effects. Conclusion: Our findings highlight a novel role of IL-10 in regulating MSC migration and cytokine secretion-associated programs, and determine the vital role of IL-10 in the domination of MSC treatment for spinal cord repair.

Hypoxia-stimulated mesenchymal stem cell-derived exosomes loaded by adhesive hydrogel for effective angiogenic treatment of spinal cord injury.

Due to the limited efficacy of current clinical treatment strategies, functional recovery after traumatic spinal cord injury (SCI) remains a knotty problem to be solved. Apart from anti-inflammation and cell replenishing treatments, accumulating evidence implies that promoting angiogenesis would also potentially benefit tissue regeneration after SCI. In this research, inspired by the role of exosomes in cell-cell communication and exosomal alteration resulting from cells under stress, exosomes were engineered through hypoxia stimulation to mesenchymal stem cells and were proposed as an alternative for promoting angiogenesis in SCI therapy. Hypoxia-stimulated exosomes (hypo-Exo) were transplanted into the injured spinal cord via encapsulation in a peptide-modified adhesive hydrogel for pro-angiogenic therapy of SCI. The adhesive peptide PPFLMLLKGSTR-modified hyaluronic acid hydrogel replenished the spinal cavity caused by SCI and achieved the local delivery of exosomes. The hypoxia-inducible factor 1-alpha content in hypo-Exo was significantly increased, resulting in the overexpression of vascular endothelial growth factor in the endothelial cells surrounding the transplant system. Ultimately, prominent angiogenesis and functional recovery after injury were demonstrated both in vitro and in vivo, indicating the immense potential of hydrogel-encapsulated hypo-Exo in treating central nervous system trauma and other ischemia diseases.