CREG1 promotes bovine placental trophoblast cells exosome release by targeting IGF2R and participates in regulating organoid differentiation via exosomes transport.

BACKGROUND: Placental exosomes are a kind of intercellular communication media secreted by placental cells during pregnancy, exosomogenesis and release are regulated by many secretory glycoproteins. CREG1 is a kind of secreted glycoprotein widely expressed in various organs and tissues of the body, which inhibits cell proliferation and enhances cell differentiation. The aim of this study was to explore the role of CREG1 in regulating exosomogenesis during the proliferation and differentiation of placental trophoblast cells in early pregnant dairy cows by targeting IGF2R and participating in regulating organoid differentiation via exosomes transport. METHODS: Molecular biological methods were firstly used to investigate the expression patterns of CREG1, IGF2R and exosomal marker proteins in early placental development of pregnant dairy cows. Subsequently, the effects of CREG1 on the formation and release of bovine placental trophoblast (BTCs) derived exosomes by targeting IGF2R were investigated. Further, the effects of CREG1 on the change of gene expression patterns along with the transport of exosomes to recipient cells and participate in regulating the differentiation of organoids were explored. RESULTS: The expression of CREG1, IGF2R and exosomal marker proteins increased with the increase of pregnancy months during the early evolution of placental trophoblast cells in dairy cows. Overexpression of Creg1 enhanced the genesis and release of exosomes derived from BTCs, while knocking down the expression of Igf2r gene not only inhibited the genesis of exosomes, but also inhibited the genesis and release of exosomes induced by overexpression of CREG1 protein. Interestingly, IGF2R can regulate the expression of CREG1 through reverse secretion. What's more, the occurrence and release of trophoblast-derived exosomes are regulated by CREG1 binding to IGF2R, which subsequently binds to Rab11. CREG1 can not only promote the formation and release of exosomes in donor cells, but also regulate the change of gene expression patterns along with the transport of exosomes to recipient cells and participate in regulating the early development of placenta. CONCLUSIONS: Our study confirmed that CREG1 is involved in the exosomogenesis and release of exosomes during the proliferation and differentiation of placental trophoblast cells in early pregnant dairy cows by targeting IGF2R, and is involved in the regulation of organoid differentiation through exosome transport.

Incremental value of 99m Tc-MIBI single-photon emission computed tomography/computed tomography fusion imaging for the diagnosis of secondary hyperparathyroidism.

PURPOSE: To assess the added value of 99m Tc-MIBI single-photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging over dual-phase scintigraphy in the diagnosis of secondary hyperparathyroidism (SHPT). METHODS: This retrospective study included 23 patients with SHPT. The diagnostic efficacy of 99m Tc-MIBI dual-phase scintigraphy and SPECT/CT fusion imaging was analyzed and compared based on the result of postoperative pathology and follow-up. To evaluate the diagnostic ability of 99m Tc-MIBI dual-phase scintigraphy, the volume and radioactive count of parathyroid lesions were assessed using the region of interest method. RESULTS: A total of 79 hyperplastic parathyroid glands and two thyroid tissues were surgically removed from 23 SHPT patients and 13 normal parathyroid glands were preserved. 99m Tc-MIBI SPECT/CT fusion imaging showed higher sensitivity and accuracy than 99m Tc-MIBI dual-phase scintigraphy [sensitivity, 77.2% (61/79) vs 46.8% (37/79); accuracy, 80.4% (74/92) vs 54.3% (50/92), respectively], but comparable specificity [100% (13/13)). Among 61 positive lesions detected by 99m Tc-MIBI SPECT/CT fusion imaging, 37 were dual-phase scintigraphy positive and 24 were dual-phase scintigraphy false negative. The radioactivity counts and radioactivity per unit volume in dual-phase scintigraphy positive were higher than that in dual-phase scintigraphy false negative ( P  < 0.05), but the volume of parathyroid lesions between the two groups had no significant difference ( P  > 0.05). CONCLUSION: Compared with 99m Tc-MIBI dual-phase scintigraphy, 99m Tc-MIBI SPECT/CT fusion imaging has incremental value in the diagnosis of SHPT. The low uptake of MIBI in the whole gland and low MIBI uptake per unit volume are easy to cause dual-phase scintigraphy false negative.

Plasma Homocysteine (Hcy) Concentration Functions as a Predictive Biomarker of SPECT-Evaluated Post-Ischemic Hyperperfusion in Acute Ischemic Stroke.

Introduction: Homocysteine (Hcy) concentration has been reported to be associated with ischemic stroke. In this study, we aimed to investigate the potential of plasma Hcy in the prediction of post-ischemic hyperperfusion in AIS patients, which was diagnosed with the single-photon emission computed tomography (SPECT) method. Methods: A total of 112 ischemic stroke patients were recruited in this study. According to whether the patients were subjected to post-ischemic hyperperfusion, all recruited subjects were divided into a post-ischemic hyperperfusion (+) group (N=48) and post-ischemic hyperperfusion (-) group (N=64). The basic demographical data, clinicopathological data and laboratory biochemical data were collected and compared. Level of homocysteine (Hcy) and cystatin-C (Cys-C) and their potential as predictive biomarker are also investigated. Results: No significant differences were spotted between the post-ischemic hyperperfusion group (+) and post-ischemic hyperperfusion (-) group in respect to the basic demographical and clinicopathological data. And the serum Hcy levels were lower in the post-ischemic hyperperfusion (+) group. Moreover, ROC analysis indicated significant relationships between Hcy levels and the onset of post-ischemic hyperperfusion. Conclusion: In conclusion, we validated that the plasma Hcy concentration can be used as a predictive biomarker of SPECT-evaluated post-ischemic hyperperfusion in patients suffering from acute ischemic stroke.