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This study aimed to investigate the effects of the human macrophage (MP) secretome in cellular xenograft rejection. The role of human nucleoside diphosphate kinase A (hNME1), from the secretome of MPs involved in the neuronal differentiation of miniature pig adipose tissue-derived mesenchymal stem cells (mp AD-MSCs), was evaluated by proteomic analysis. Herein, we first demonstrate that hNME1 strongly binds to porcine ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 (pST8SIA1), which is a ganglioside GD3 synthase. When hNME1 binds with pST8SIA1, it induces degradation of pST8SIA1 in mp AD-MSCs, thereby inhibiting the expression of ganglioside GD3 followed by decreased neuronal differentiation of mp AD-MSCs. Therefore, we produced nanobodies (NBs) named NB-hNME1 that bind to hNME1 specifically, and the inhibitory effect of NB-hNME1 was evaluated for blocking the binding between hNME1 and pST8SIA1. Consequently, NB-hNME1 effectively blocked the binding of hNME1 to pST8SIA1, thereby recovering the expression of ganglioside GD3 and neuronal differentiation of mp AD-MSCs. Our findings suggest that mp AD-MSCs could be a potential candidate for use as an additive, such as an immunosuppressant, in stem cell transplantation.

Gangliosides are sialic acid-containing glycosphingolipids, which are the most abundant family of glycolipids in eukaryotes. Gangliosides have been suggested to be important lipid molecules required for the control of cellular procedures, such as cell differentiation, proliferation, and signaling. GD1a is expressed in interstitial cells during ovarian maturation in mice and exogenous GD1a is important to oocyte maturation, monospermic fertilization, and embryonic development. In this context, GM1 is known to influence signaling pathways in cells and is important in sperm−oocyte interactions and sperm maturation processes, such as capacitation. GM3 is expressed in the vertebrate oocyte cytoplasm, and exogenously added GM3 induces apoptosis and DNA injury during in vitro oocyte maturation and embryogenesis. As a consequence of this, ganglioside GT1b and GM1 decrease DNA fragmentation and act as H2O2 inhibitors on germ cells and preimplantation embryos. This review describes the functional roles of gangliosides in spermatozoa, oocytes, and early embryonic development.

Improvement in quality of life (QoL) is a primary treatment goal for patients with peripheral arterial disease (PAD). The current study aimed to quantify improvement in the health status of PAD patients following peripheral revascularization using the peripheral artery questionnaire (PAQ) and ankle-brachial index (ABI), and to evaluate possible correlation between the two methods. The PAQ and ABI were assessed in 149 symptomatic PAD patients before, and three months after peripheral revascularization. Mean PAQ summary scores improved significantly three months after revascularization (+49.3 ± 15 points, p &lt, 0.001). PAQ scores relating to patient symptoms showed the largest improvement following revascularization. The smallest increases were seen in reported treatment satisfaction (all p’s &lt, 0.001). As expected the ABI of treated limbs showed significant improvement post-revascularization (p &lt, 0.001). ABI after revascularization correlated with patient-reported changes in the physical function and QoL domains of the PAQ. Twenty-two percent of PAD patients were identified as having a poor response to revascularization (increase in ABI &lt, 0.15). Interestingly, poor responders reported improvement in symptoms on the PAQ, although this was less marked than in patients with an increase in ABI &gt, 0.15 following revascularization. In conclusion, data from the current study suggest a significant correlation between improvement in patient-reported outcomes assessed by PAQ and ABI in symptomatic PAD patients undergoing peripheral revascularization.