Corrigendum: A progression analysis of motor features in Parkinson's disease based on the mapper algorithm.

[This corrects the article DOI: 10.3389/fnagi.2023.1047017.].

A progression analysis of motor features in Parkinson's disease based on the mapper algorithm.

Background: Parkinson's disease (PD) is a neurodegenerative disease with a broad spectrum of motor and non-motor symptoms. The great heterogeneity of clinical symptoms, biomarkers, and neuroimaging and lack of reliable progression markers present a significant challenge in predicting disease progression and prognoses. Methods: We propose a new approach to disease progression analysis based on the mapper algorithm, a tool from topological data analysis. In this paper, we apply this method to the data from the Parkinson's Progression Markers Initiative (PPMI). We then construct a Markov chain on the mapper output graphs. Results: The resulting progression model yields a quantitative comparison of patients' disease progression under different usage of medications. We also obtain an algorithm to predict patients' UPDRS III scores. Conclusions: By using mapper algorithm and routinely gathered clinical assessments, we developed a new dynamic models to predict the following year's motor progression in the early stage of PD. The use of this model can predict motor evaluations at the individual level, assisting clinicians to adjust intervention strategy for each patient and identifying at-risk patients for future disease-modifying therapy clinical trials.

Rab37 Promotes Endothelial Differentiation and Accelerates ADSC-Mediated Diabetic Wound Healing through Regulating Secretion of Hsp90α and TIMP1.

Accumulating evidence indicates that adipose tissue-derived mesenchymal stem cells (ADSCs) are an effective treatment for diabetic refractory wounds. However, the application of ADSCs to diabetic wounds is still limited, indicating that we still lack sufficient knowledge regarding regulators/mediators of ADSCs during wound healing. Rab37, a member of RabGTPase, may function as regulator of vesicle trafficking, which is a crucial event for the secretion of cytokines by ADSCs. Our previous study indicated that Rab37 promotes the adiopogenic differentiation of ADSCs. In this study, we explored the role of Rab37 in ADSC-mediated diabetic wound healing. An in vivo study in db/db diabetic mice showed that Rab37-expressing ADSCs shortened the wound closure time, improved re-epithelialization and collagen deposition, and promoted angiogenesis during wound healing. An in vitro study showed that Rab37 promoted the proliferation, migration and endothelial differentiation of ADSCs. LC-MS/MS analysis identified Hsp90α and TIMP1 as up-regulated cytokines in conditioned media of Rab37-ADSCs. The up-regulation of Rab37 enhanced the secretion of Hsp90α and TIMP1 during endothelial differentiation and under high-glucose exposure. Interestingly, Rab37 promoted the expression of TIMP1, but not Hsp90α, during endothelial differentiation. PLA showed that Rab37 can directly bind to Hsp90α orTIMP1 in ADSCs. Moreover, Hsp90α and TIMP1 knockdown compromised the promoting effects of Rab37 on the proliferation, migration and endothelial differentiation of ADSCs. In conclusion, Rab37 promotes the proliferation, migration and endothelial differentiation of ADSCs and accelerates ADSC-mediated diabetic wound healing through regulating the secretion of Hsp90α and TIMP1.

RAB37 Promotes Adipogenic Differentiation of hADSCs via the TIMP1/CD63/Integrin Signaling Pathway.

The adipogenic differentiation ability of human adipose-derived mesenchymal stem cells (hADSCs) is critical for the construction of tissue engineering adipose, which shows promising applications in plastic surgery and regenerative medicine. RAB37 is a member of the small RabGTPase family and plays a critical role in vesicle trafficking. However, the role of RAB37 in adipogenic differentiation of hADSCs remains unclear. Here, we report that both the mRNA and protein levels of RAB37 fluctuated during adipogenic differentiation. Upregulation of RAB37 was observed at the early stage of adipogenic differentiation, which was accompanied by increased expression of transcription factors PPARγ2 and C/EBPα, and lipoprotein lipase (LPL). Overexpression of RAB37 promoted adipogenesis of hADSCs, as revealed by Oil Red O staining and increased expression of PPARγ2, C/EBPα, and LPL. Several upregulated cytokines related to RAB37-mediated adipogenic differentiation were identified using a cytokine array, including tissue inhibitor of matrix metalloproteinase 1 (TIMP1). ELISA confirmed that upregulation of RAB37 increased the secretion of TIMP1 by hADSCs. Proximity ligation assay showed that RAB37 interacts with TIMP1 directly. Knockdown of TIMP1 compromised RAB37-mediated adipogenic differentiation. In addition, TIMP1 binds membrane receptor CD63 and integrin ß1. RAB37 promotes Tyr397 phosphorylation of FAK, an important protein kinase of the integrin ß1 signaling. Moreover, both knockdown of CD63 and inhibitor of FAK impeded RAB37-mediated adipogenic differentiation. In conclusion, RAB37 positively regulates adipogenic differentiation of hADSCs via the TIMP1/CD63/integrin ß1 signaling pathway.

Response of pearl oyster Pinctada fucata martensii to allograft-induced stress from lipid metabolism.

The pearl oyster, Pinctada fucata martensii, produces high-quality pearls. During pearl production, excess immune and inflammatory response after transplantation will lead to nucleus rejection, pearl sac formation failure, and death of the host pearl oyster. The hemocyte transcriptome and fatty acid (FA) contents in the adductor muscle before and after transplantation were analyzed to investigate the response of pearl oyster P. f. martensii to allograft-induced stress from lipid metabolism. The hemocyte transcriptome analysis detected 193 lipid metabolism-related genes, such as the elongation of very long-chain FA protein 5, acyl-CoA 6-desaturase, cytochrome P450, phospholipase A2, glycerol-3-phosphate O-acyltransferase, and prostaglandin-H2 d-isomerase. Pathway enrichment analyses revealed that these genes were mainly involved in the "biosynthesis of unsaturated FAs," "FA biosynthesis," "ARA metabolism," and "glycerolipid metabolism." An analysis of FA contents in the adductor muscle indicated no significant difference in the contents of lauric acid, myristic acid, pentadecanoic acid, palmitic acid, palmitoleic acid, heptadecanoic acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, arachidic acid, α-linolenic acid, eicosadienoic acid, docosadienoic acid, and 11,14,17-eicosatrienoic acid. However, ARA, DHA, and EPA in the adductor muscle after transplantation were significantly greater than those processed without grafting surgery. These results suggest that pearl oysters require more polyunsaturated FAs (PUFAs) to regulate their inflammatory and immune response after transplantation. However, their ability to biosynthesize unsaturated FAs is limited. Given these results, the addition of PUFA-containing diets or selection of a line with strong ability to biosynthesize unsaturated FAs may be valuable for pearl oyster recovery after transplantation.

[Observation of course of placental separation by continuous dynamic ultrasonography during third stage of labor].

OBJECTIVE: To investigate the physiologic course of third stage of labor, and to judge the optimal time of natural placental separation permitted. METHODS: To observe and record the course of third stage of labor by continuous dynamic ultrasonography and to estimate the total amount of blood loss from placental separation within two hours after delivery by the method of weighing lost blood. RESULTS: Third stage of labor can be divided into four phases: the latent phase (4.37 +/- 3.78) min, the contraction phase (1.48 +/- 0.97) min, the detachment phase (0.50 +/- 0.00) min, and the expulsion phase (0.62 +/- 2.23) min. In 85% of the puerperas the third stage of labor takes about 10 minutes (average 6.94 minutes). The amount of postpartum hemorrhage and the risk of the patient increased prominently if the time of stage of labor was longer than 10 minutes (P < 0.01). CONCLUSION: The third stage of labor must be limited in 10 minutes to prevent postpartum hemorrhage.