Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity.

During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

Research on the Specificity of Electrophysiological Signals of Human Acupoints Based on the 90-Day Simulated Weightlessness Experiment on the Ground.

Acupoint specificity for diseases has consistently been the focus of acupuncture research owing to its excellent prospects for clinical diagnosis and treatment. However, the specificity of cardiovascular and sleep functions in terms of electrical signals at acupoints remains unclear. In this study, five volunteers were recruited and their electrophysiological signals of GV20 (baihui), RN17 (danzhong), PC6 (neiguan), and SP6 (sanyinjiao) and the corresponding sham points, Pittsburgh sleep quality index, blood pressure, and echocardiography were monitored over four periods of 90-day head-down bed rest (HDBR). The results demonstrated that the power and characteristic amplitude of the acupoints were more significant than those of the sham points under normal conditions. And along with the altered physiological condition of the body after HDBR, the differential signal characteristic amplitude (DSCA) and the power of the acupoints were decreased to a larger extent than those of the sham points. In addition, the difference between the power of acupuncture and sham points was also reduced. During the recovery period, except for GV20, the power and DSCA of other acupoints did not return to normal. In terms of DSCA, GV20 is related to human sleep function and other acupoints are related to cardiovascular function. The above results show that the electrophysiological signals of acupoints are disease-specific and more accurately reflect the changes of physiological homeostasis. The research conduces to the development of acupuncture-based disease diagnosis and treatment integrated methods, and the realization of the portable and accurate diagnosis and regulation of diseases in space medicine.

Exploring the Effect of Ginsenoside Rh1 in a Sleep Deprivation-Induced Mouse Memory Impairment Model.

Panax ginseng C.A. Meyer (Araliaceae) has been used in traditional Chinese medicine for enhancing cognition for thousands of years. Ginsenoside Rh1, a constituent of ginseng root, as with other constituents, has memory-improving effects in normal mice and scopolamine-induced amnesic mice. Sleep deprivation (SD) is associated with memory impairment through induction of oxidative stress. The present study investigated the effect of Rh1 against SD-induced cognitive impairment and attempted to define the possible mechanisms involved. Ginsenoside Rh1 (20 µmol/kg; 40 µmol/kg) and modafinil (0.42 g/kg) were administered to the mice intraperitoneally for 23 days. After 14-day SD, locomotor activity was examined using the open field test, and the object location recognition and Morris water maze tests were used to evaluate cognitive ability. The cortex and hippocampus were then dissected and homogenized, and levels and activities of antioxidant defense biomarkers were evaluated to determine the level of oxidative stress. The results revealed that Rh1 prevented cognitive impairment induced by SD, and its ability to reduce oxidative stress in cortex and hippocampus may contribute to the mechanism of action. Copyright © 2017 John Wiley & Sons, Ltd.

Kai Xin San aqueous extract improves Aß1-40-induced cognitive deficits on adaptive behavior learning by enhancing memory-related molecules expression in the hippocampus.

ETHNOPHARMACOLOGICAL RELEVANCE: Kai Xin San (KXS), a traditional formula of Chinese medicine, has been used to treat dementia. AIM OF THE STUDY: The present study aimed to investigate its ameliorating effects on Aß1-40-induced cognitive impairment in rats using a series of novel reward-directed instrumental learning tasks, and to determine its possible mechanism of action. MATERIALS AND METHODS: Rats were pretreated with KXS aqueous extract (0.72 and 1.44g/kg, p.o.) for 10 days, and were trained to gain reward reinforcement by lever pressing at the meantime. Thereafter, rats received a bilateral microinjection of Aß1-40 in CA1 regions of the hippocampus. Cognitive performance was evaluated with the goal directed (higher response ratio) and habit (visual signal discrimination and extinction) learning tasks, as well as on the levels of memory-related biochemical parameters and molecules. RESULTS: Our findings first demonstrated that KXS can improve Aß1-40-induced amnesia in RDIL via enhancing the comprehension of action-outcome association and the utilization of cue information to guide behavior. Then, its ameliorating effects should be attributed to the modulation of memory-related molecules in the hippocampus. CONCLUSION: In conclusion, KXS has the potential to prevent and/or delay the deterioration of cognitive impairment in AD.

Tong Luo Jiu Nao ameliorates Aß1-40-induced cognitive impairment on adaptive behavior learning by modulating ERK/CaMKII/CREB signaling in the hippocampus.

BACKGROUND: Tong Luo Jiu Nao (TLJN), a modern formula of Chinese medicine extracts on the basis of Traditional Chinese Medicine theory, has been used to treat dementia. The present study aimed to investigate its ameliorating effects on Aß1-40-induced cognitive impairment in rats using a series of novel reward-directed instrumental learning (RDIL) tasks, and to determine its possible mechanism of action. METHODS: Rats were pretreated with TLJN extract (0.9 and 1.8 g/kg, p.o.) for 10 daysbefore surgery, and were trained to gain reward reinforcement by lever pressing at the meantime. Thereafter, rats received a bilateral microinjection of Aß1-40 in CA1 regions of the hippocampus. Cognitive performance was evaluated with the goal directed (higher response ratio) and habit (visual signal discrimination and extinction) learning tasks, as well as on the levels of biochemical parameters and molecules. RESULTS: Our findings first demonstrated that TLJN can improve Aß1-40-induced amnesia in RDIL via enhancing the comprehension of action-outcome association and the utilization of cue information to guide behavior. Then, its ameliorating effects should attribute to the modulation of ERK/CaMKII/CREB signaling in the hippocampus. CONCLUSION: TLJN can markedly enhance cognitions of Aß1-40 microinjection animal model in adaptive behavioral tasks. It has the potential, possibly as complementary and alternative therapy, to prevent and/or delay the deterioration of cognitive impairment in AD.

Antidepressant-like effects and mechanism of action of SYG in depression model in rats.

OBJECTIVES: The present study aimed to evaluate whether SYG, a Chinese herbal formula, could produce antidepressant-like effects in learned helplessness (LH) model and chronic mild stress (CMS) model in rats. The mechanism underlying the antidepressant-like action was investigated by exploring BDNF signaling way in the hippocampus. MATERIAL AND METHODS: SYG was administrated for 5 consecutive days (100 and 200 mg/kg/day, intragastrically) in the learned helplessness model; SYG was administered daily by gastric gavages during both the 5-week stress session and behavior tests periods in the chronic mild stress model (100 and 200 mg/kg). The serum corticosterone level was measured in the learned helplessness model. Levels of BDNF and Tyrosine-related kinase B (TrkB), were evaluated in the hippocampus of chronic mild stress model. RESULTS: A deficit in avoidance learning and higher corticosterone level were observed in learned helplessness rats. SYG significantly reduced this deficit and reversed the corticosterone alteration. CMS induced significant reduction of sucrose intake in the sucrose preference test, an increased latency to feed in the novelty-suppressed feeding test and an increased immobility time in the forced swim test as compared to the control. It was also found that BDNF and TrkB levels were decreased in CMS model. Chronic treatment of SYG significantly suppressed the behavioral changes and up-regulated the BDNF signal pathway in the hippocampus. CONCLUSION: Our results suggest that SYG alleviates depression induced by LH and CMS model. The antidepressant-like activity of SYG is likely mediated by activation the BDNF signal pathway in the hippocampus.