Hippocampal Mitochondrial Transplantation Alleviates Age-Associated Cognitive Decline via Enhancing Wnt Signaling and Neurogenesis.

Gradual cognition decline and mitochondrial dysfunction are two notable changes closely associated with aging. Enhancing mitochondrial function has been assumed to be antiaging. However, most current mitochondria-promoting agents usually target 1-2 aspects of mitochondrial function. In the present study, we transplanted mitochondria isolated from young mice into the hippocampus of aged mice, which presumably boost mitochondrial function more thoroughly, examined the effects on cognition, and explored the possible underlying mechanism. Our data showed that exogenous mitochondria were efficiently internalized by nestin-positive neural progenitors in the hippocampus. Mitochondrial transplantation quickly increased ATP levels, enhanced the activity of mitochondrial complexes I, II, and IV, and decreased Tom20 expression in the hippocampus. In regard of cognitive function, mitochondria-treated mice displayed a remarkable improvement of novel object recognition and spatial memory. Utilizing the Wnt signaling reporting mouse line, TOPGAL mice, we detected activated canonical Wnt signaling in the neural progenitors of the mitochondria-treated hippocampus. Further, BrdU labeling showed that exogenous mitochondria significantly stimulated neural progenitor neurogenesis and proliferation. Taken together, our data demonstrated that exogenous mitochondria from young mice might be a novel way of rejuvenating the function of hippocampal neural progenitors to exert antiaging effects.

Characteristics, Prognosis, and Competing Risk Nomograms of Cutaneous Malignant Melanoma: Evidence for Pigmentary Disorders.

Purpose: Cutaneous malignant melanoma (CMM) always presents as a complex disease process with poor prognosis. The objective of the present study was to explore the influence of solitary or multiple cancers on the prognosis of patients with CMM to better understand the landscape of CMM. Methods: We reviewed the records of CMM patients between 2004 and 2015 from the Surveillance, Epidemiology, and End Results Program. The cumulative incidence function was used to represent the probabilities of death. A novel causal inference method was leveraged to explore the risk difference to death between different types of CMM, and nomograms were built based on competing risk models. Results: The analysis cohort contained 165,043 patients with CMM as the first primary malignancy. Patients with recurrent CMM and multiple primary tumors had similar overall survival status (p = 0.064), while their demographics and cause-specific death demonstrated different characteristics than those of patients with solitary CMM (p < 0.001), whose mean survival times are 75.4 and 77.3 months and 66.2 months, respectively. Causal inference was further applied to unveil the risk difference of solitary and multiple tumors in subgroups, which was significantly different from the total population (p < 0.05), and vulnerable groups with high risk of death were identified. The established competing risk nomograms had a concordance index >0.6 on predicting the probabilities of death of CMM or other cancers individually across types of CMM. Conclusion: Patients with different types of CMM had different prognostic characteristics and different risk of cause-specific death. The results of this study are of great significance in identifying the high risk of cause-specific death, enabling targeted intervention in the early period at both the population and individual levels.