Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy.

Adoptive immunotherapy in the T cell landscape exhibits efficacy in cancer treatment. Over the past few decades, genetically modified T cells, particularly chimeric antigen receptor T cells, have enabled remarkable strides in the treatment of hematological malignancies. Besides, extensive exploration of multiple antigens for the treatment of solid tumors has led to clinical interest in the potential of T cells expressing the engineered T cell receptor (TCR). TCR-T cells possess the capacity to recognize intracellular antigen families and maintain the intrinsic properties of TCRs in terms of affinity to target epitopes and signal transduction. Recent research has provided critical insight into their capability and therapeutic targets for multiple refractory solid tumors, but also exposes some challenges for durable efficacy. In this review, we describe the screening and identification of available tumor antigens, and the acquisition and optimization of TCRs for TCR-T cell therapy. Furthermore, we summarize the complete flow from  laboratory to clinical applications of TCR-T cells. Last, we emerge future prospects for improving therapeutic efficacy in cancer world with combination therapies or TCR-T derived products. In conclusion, this review depicts our current understanding of TCR-T cell therapy in solid neoplasms, and provides new perspectives for expanding its clinical applications and improving therapeutic efficacy.

Signalling pathways underlying pulsed electromagnetic fields in bone repair.

Pulsed electromagnetic field (PEMF) stimulation is a prospective non-invasive and safe physical therapy strategy for accelerating bone repair. PEMFs can activate signalling pathways, modulate ion channels, and regulate the expression of bone-related genes to enhance osteoblast activity and promote the regeneration of neural and vascular tissues, thereby accelerating bone formation during bone repair. Although their mechanisms of action remain unclear, recent studies provide ample evidence of the effects of PEMF on bone repair. In this review, we present the progress of research exploring the effects of PEMF on bone repair and systematically elucidate the mechanisms involved in PEMF-induced bone repair. Additionally, the potential clinical significance of PEMF therapy in fracture healing is underscored. Thus, this review seeks to provide a sufficient theoretical basis for the application of PEMFs in bone repair.

miR-27a-3p targets NR5A2 to regulate CYP19A1 expression and 17-ß estradiol synthesis in ovine granulosa cells.

Although 17-ß estradiol (E2) synthesis is important in regulating female fertility, we know little regarding the molecular mechanism of miRNA-regulated ovine E2 synthesis. Here, our experiments with granulosa cells (GCs) from Hu sheep revealed miR-27a-3p involvement in E2 synthesis and its association with ovine litter size. First, we showed that miR-27a-3p of sheep and other mammals share a high nucleotide identity. Next, gain- and loss-of-function assays indicated that miR-27a-3p inhibits CYP19A1 expression and E2 synthesis in GCs. Moreover, we demonstrated that NR5A2 is a direct target of miR-27a-3p. Ovine miR-27a-3p suppresses E2 synthesis via the NR5A2 and CYP19A1 axes. We also identified four single nucleotide polymorphisms in the ovine miR-27a gene, and g.-13 G>A and g 0.24 T > G were significantly associated with the first and the second parity litter size, respectively (P < 0.05). In summary, our findings reveal that miR-27a-3p is a novel regulator of E2 synthesis and may predict litter size of Hu sheep, providing insight into mechanisms underlying granulosa cell function and female fertility.