Accommodation and Binocular Vision in Children with Myopic Anisometropia.

Purpose: To assess the differences in accommodation and binocular vision in children with myopic anisometropia and determine the correlation with anisometropia. Method: A total of 110 patients with myopia aged 8-15 years were recruited from June 2021 to February 2022 from the Affiliated Hospital of Xuzhou Medical University. Based on the interocular differences of spherical equivalent refraction, patients were divided into the isometropia (35 children), low anisometropia (LA group, 42 children), and high anisometropia (HA group, 33 children). The variables assessed were refraction, heterophoria, amplitude of accommodation (AMP), accommodative response (AR), gradient AC/A, positive and negative relative accommodation (PRA/NRA), and near stereopsis in the three groups. Pearson's correlation coefficient tests were used to investigate the possible association between each parameter and interocular differences (IODs). Results: Among 110 subjects, there were 49 males and 61 females with a mean age of 11.39 ± 2.28 years. Compared with those in the isometropia group, AMP was lower and near stereopsis was higher in the LA group, and the distance and near heterophoria, PRA, AR, and near stereopsis were higher, and PRA, AMP, and gradient AC/A were lower in the HA group (all P < 0.05). Compared with those in the LA group, the near stereopsis, AR, and the near stereopsis were higher in the HA group, and the gradient AC/A was lower (all P < 0.05). However, no significant differences existed in the negative relative accommodation (P > 0.05). The distance and near heterophoria, AR, AMP, and near stereopsis were observed to be correlated with IODs, respectively (r = -0.259, p = 0.006; r = -0.201, p = 0.036; r = 0.306, p = 0.001; r = -0.315, p = 0.001; r = 0.535, p < 0.001). Conclusion: Our results suggested that with the increase of anisometropia, distance and near heterophoria, AR, AMP, and near stereopsis had a tendency to get worse in children with myopic anisometropia.

Exercise preconditioning promotes myocardial GLUT4 translocation and induces autophagy to alleviate exhaustive exercise-induced myocardial injury in rats.

Exercise preconditioning (EP) is a line of scientific inquiry into the short-term biochemical mediators of cardioprotection in the heart. This study examined the involvement of autophagy induced by energy metabolism in myocardial remodelling by EP and myocardial protection. A total of 120 healthy male Sprague Dawley (SD) rats were randomly divided into six groups. Plasma cTnI, HBFP staining and electrocardiographic indicators were examined in the context of myocardial ischemic/hypoxic injury and protection. Western blotting and fluorescence double labelling were used to investigate the relationship between energy metabolism and autophagy in EP-resistant myocardial injury caused by exhaustive exercise. Compared with those in the C group, the levels of myocardial ischemic/hypoxic injury were significantly increased in the EE group. Compared with those in the EE group, the levels of myocardial ischemic/hypoxic injury were significantly decreased in the EEP + EE and LEP + EE groups. Compared with that in the EE group, the level of GLUT4 in the sarcolemma was significantly increased, and the colocalization of GLUT4 with the sarcolemma was significantly increased in the EEP + EE and LEP + EE groups (P < 0.05). LC3-II and LC3-II/LC3-I levels of the EEP + EE group were significantly elevated compared with those in the EE group (P < 0.05). The levels of p62 were significantly decreased in the EEP + EE and LEP + EE groups compared with the EE group (P < 0.05). EP promotes GLUT4 translocation and induced autophagy to alleviate exhaustive exercise-induced myocardial ischemic/hypoxic injury.

Exercise preconditioning improves electrocardiographic signs of myocardial ischemic/hypoxic injury and malignant arrhythmias occurring after exhaustive exercise in rats.

Exercise preconditioning (EP) has a good myocardial protective effect. This study explored whether EP improves electrocardiographic (ECG) signs of myocardial ischemic/hypoxic injury and the occurrence of malignant arrhythmia after exhaustive exercise. A total of 120 male SD rats were randomly divided into the control group (group C), early exercise preconditioning group (group EEP), late exercise preconditioning group (group LEP), exhaustive exercise group (group EE), early exercise preconditioning + exhaustive exercise group (group EEP + EE) and late exercise preconditioning + exhaustive exercise group (group LEP + EE). Changes in heart rate (HR), ST segment, T wave and QT corrected (QTc) intervals on ECG; hematoxylin-basic fuchsin-picric acid (HBFP) staining; and cTnI levels were used to study myocardial injury and the protective effect of EP. Compared with those in group C, the levels of plasma markers of myocardial injury, HBFP staining and ECG in group EE were significantly increased (P < 0.05). Compared with those in group EE, the levels of plasma markers of myocardial injury, HBFP staining and ECG in group EEP + EE and group LEP + EE were significantly decreased (P < 0.05). The results suggested that EP improved ECG signs of myocardial ischemic/hypoxic injury and malignant arrhythmias that occur after exhaustive exercise. The ST segment and T wave could also serve as indexes for evaluating exhaustive exercise-induced myocardial ischemia/hypoxia.

[Multi-omics analysis of regulating effects of hyperoside on lipid metabolism in high-fat diet mice].

The aim of this study was to explore the regulating effects of hyperoside (Hyp) on lipid metabolism in high-fat diet mice. The high-fat diet mouse model was established by high-fat diet induction. After 5 weeks of Hyp intragastric administration in high-fat diet mice, the serum lipid levels before and after Hyp administration were measured by the corresponding kits. The tissue structure of mouse liver was observed by HE staining before and after Hyp administration. The changes of intestinal flora and transcriptome were measured by Illumina platforms. Liquid chromatography-mass spectrometry (LC-MS) was used to determine non-targeted metabolites. The results showed that Hyp significantly reduced lipid levels in the high-fat diet mice and effectively restored the external morphology and internal structure of liver tissue. Hyp changed the species composition of the intestinal flora in high-fat diet mice, increased the abundance of beneficial flora such as Ruminococcus, and decreased the abundance of harmful flora such as Sutterella. Combined multi-omics analysis revealed that the effect of retinoic acid on lipid metabolism was significant in the high-fat diet mice treated with Hyp, while the increase of retinoic acid content was significantly negatively correlated with the expression of genes such as cyp1a2 and ugt1a6b, positively correlated with AF12 abundance, and significantly negatively correlated with unidentified_Desulfovibrionaceae abundance. These results suggest that Hyp may modulate the abundance of AF12, unidentified_Desulfovibrionaceae and inhibit the expression of genes such as cyp1a2 and ugt1a6b, thus increasing the content of retinoic acid and regulating lipid metabolism in the high-fat diet mice.

Exercise Preconditioning Promotes Autophagy to Cooperate for Cardioprotection by Increasing LC3 Lipidation-Associated Proteins.

The cardioprotection of exercise preconditioning (EP) has been well documented. EP can be divided into two phases that are the induction of exercise preconditioning (IEP) and the protection of exercise preconditioning (PEP). PEP is characterized by biphasic protection, including early exercise preconditioning (EEP) and late exercise preconditioning (LEP). LC3 lipidation-mediated autophagy plays a pivotal role in cardioprotection. This study aimed to investigate the alterations of LC3 lipidation-associated proteins during EP-induced cardioprotection against myocardial injury induced by exhaustive exercise (EE) was used in a rat model of EP. These rats were subjected to an intermittent exercise consisting of four periods, with each period including 10 min of running at 30 m/min and 0% grade (approximately 75% VO2max) followed by 10 min of intermittent rest. A model of EE-induced myocardial injury was developed by subjecting rats to a consecutive running (30 m/min, 0% grade) till exhaustion. Following EEP, the colocalization of LC3 with Atg7 was significantly increased, and LC3-I, LC3-II, LC3-II/LC3-I, Atg7, Atg4B, and Atg3 levels were significantly increased. Atg7, Atg4B, and Atg3 mRNAs were all significantly upregulated, and LC3 mRNAs tended to be higher. Following LEP, Atg4B, and Atg3 levels were significantly increased. Atg7, Atg4B, and Atg3 mRNAs were all significantly upregulated, and LC3 mRNAs tended to be higher. A group of rats were subjected to EEP followed by EE, and the co-localization of LC3 with Atg7 was significantly increased, while LC3-I, LC3-II, LC3-II/LC3-I, Atg7, Atg4B, and Atg3 levels were also significantly increased. Moreover, there was a significant increase in the co-localization of LC3 with Atg7, LC3-I, LC3-II, Atg7, and Atg4B levels during LEP followed by EE. The formation of autophagosome during LEP followed by EE may have been weaker than that during EEP followed by EE due to the lower lipidation of LC3. EP may promote autophagy to maintain cell homeostasis and survival, which cooperates for cardioprotection of alleviating exhaustive exercise-induced myocardial injury by increasing LC3 lipidation-associated proteins. There is a difference between EEP and LEP in terms of the mechanisms of cardioprotection afforded by these respective conditions. The positive regulation of transcription and translation level of LC3 lipidation-associated proteins may all be involved in the mechanism of EEP and LEP, while compared with LEP, the regulation of translation level of EEP is more positively to promote autophagy.

Exercise Preconditioning Increases Beclin1 and Induces Autophagy to Promote Early Myocardial Protection via Intermittent Myocardial Ischemia-Hypoxia.

Exercise preconditioning (EP) provides protective effects for acute cardiovascular stress; however, its mechanisms need to be further investigated. Autophagy is a degradation pathway essential for myocardium health. Therefore, we investigated whether intermittent myocardial ischemia-hypoxia affected Beclin1 and whether the changes in autophagy levels contribute to EP-induced early myocardial protective effects. Rats were trained on a treadmill using an EP model (four cycles of 10 minutes of running/10 minutes of rest). Exhaustive exercise (EE) was performed to induce myocardial injury. Cardiac troponin I (cTnI) and ischemia-hypoxia staining were used to evaluate myocardial injury and protection. Double-labeled immunofluorescence staining and western blot analysis were employed to examine related markers. EP attenuated the myocardial ischemic-hypoxic injury induced by EE. Compared with the control (C) group, the dissociations of Beclin1/Bcl-2 ratio and Beclin1 expression were both higher in all other groups. Compared with the C group, PI3KC3 and the LC3-II/LC3-I ratio were higher in all other groups, whereas LC3-II was higher in the EE and EEP + EE groups. p62 was higher in the EE group than in the C group but lower in the EEP + EE group than in the EE group. We concluded that EP increases Beclin1 via intermittent myocardial ischemia-hypoxia and induces autophagy, which exerts early myocardial protective effects and reduces the myocardial ischemic-hypoxic injury induced by exhaustive exercise.

Comparison of myocardial ischemic/hypoxic staining techniques for evaluating the alleviation of exhaustive exercise-induced myocardial injury by exercise preconditioning.

Exercise preconditioning (EP) can alleviate myocardial ischemic/hypoxic injury by inducing endogenous cardioprotection. Hematoxylin-eosin (HE), hematoxylin-basic fuchsin-picric acid (HBFP), and chromotrope-2R brilliant green (C-2R BG) staining have been used to visualize myocardial ischemic/hypoxic changes in previous EP studies, but comprehensive evaluation and comparisons of these methods are lacking. This study evaluated ischemic/hypoxic changes in adjacent myocardial sections by HE, HBFP, and C-2R BG and compared the characteristics of sections stained by these three methods to show changes associated with exercise-induced myocardial ischemic/hypoxic injury. Rats were randomly divided into four groups: control (C), exercise preconditioning (EP), exhaustive exercise (EE), and exercise preconditioning + exhaustive exercise (EP + EE). Adjacent myocardial sections were stained as described above and compared to evaluate the effects of exercise-induced myocardial ischemic/hypoxic injury. The three staining methods revealed consistent localization patterns of myocardial ischemic/hypoxic injury in all groups. Results suggest that EP can alleviate exhaustive exercise-induced myocardial ischemic/hypoxic injury, and the three staining methods are suitable for the histological study of exercise-induced myocardial ischemic/hypoxic injury and protection. HE staining is a simple procedure but is not specific for myocardial ischemic/hypoxic injury. HBFP and C-2R BG staining can be used to specifically visualize myocardial ischemic/hypoxic injury.

Manufacture and clinical application of the forearm pronation's assistant tableware in the severely burned.

INTRODUCTION: Even after reconstructive surgery, it is still difficult for patients with severe burns to achieve independent eating activity. In this project, we customized the forearm pronation's assistant tableware to assist in improvement with eating activities. METHODS: From January 2017 to December 2018, 28 patients with severe burns including the hands were recruited. For the patient's independent eating activities, we customized forearm pronation's tableware (forks and spoons). We compared modified Barthel index (MBI) and Visual analogue scale (VAS) of satisfaction under three conditions: no auxiliary tableware, ADL universal cuff, or forearm pronation tableware; to compare the duration and the weight of food spilled during lunch when the patients wore the ADL universal cuff or the forearm pronation's tableware. Differences in MBI (rank data) were tested by the Friedman test, differences in VAS (normal distribution) were tested with One-way ANOVA (Bonferroni), differences in the duration and the weight (normal distribution data) were tested by paired sample t test. RESULTS: After wearing the forearm pronation's assistant tableware, MBI VAS both increased more than when the patients did not wear the auxiliary tableware (all p＜0.05). When the subjects wore forearm pronation tableware, the duration of lunch significantly decreased and the quality of eating activity significantly improved compared to the ADL universal cuff in eating activity (all p＜0.05). CONCLUSION: After wearing the forearm pronation's assistant tableware, the patients with severe burns completely or almost completely accomplished independent eating, the duration was decreased, and during eating activity the quality and the satisfaction were improved. CLINICAL TRIAL REGISTRATION: Chinese Clinical trial registry, ChiCTR1800019963.

Altered expression levels of autophagy-associated proteins during exercise preconditioning indicate the involvement of autophagy in cardioprotection against exercise-induced myocardial injury.

Exercise has been reported to induce autophagy. We hypothesized that exercise preconditioning (EP)-related autophagy in cardiomyocytes could be attributed to intermittent ischemia-hypoxia, allowing the heart to be protected for subsequent high-intensity exercise (HE). We applied approaches, chromotrope-2R brilliant green (C-2R BG) staining and plasma cTnI levels measuring, to characterize two periods of cardioprotection after EP: early EP (EEP) and late EP (LEP). Further addressing the relationship between ischemia-hypoxia and autophagy, key proteins, Beclin1, LC3, Cathepsin D, and p62, were determined by immunohistochemical staining, western blotting, and by their adjacent slices with C-2R BG. Results indicated that exercise-induced ischemia-hypoxia is a key factor in Beclin1-dependent autophagy. High-intensity exercise was associated with the impairment of autophagy due to high levels of LC3II and unchanged levels of p62, intermittent ischemia-hypoxia by EP itself plays a key role in autophagy, which resulted in more favorable cellular effects during EEP-cardioprotection compared to LEP.

Changes in Autophagy Levels in Rat Myocardium During Exercise Preconditioning-Initiated Cardioprotective Effects.

The role of autophagy in the cardioprotection conferred by ischemic preconditioning (IPC) has been well described. This study aimed to investigate the changes in autophagy levels during the cardioprotective effects initiated by exercise preconditioning (EP).Rats were randomly divided into 4 groups: group C (control), group EP, group EE (exhaustive exercise), and group EP + EE (EP pretreatment at 0.5 hours before EE). The EP protocol included 4 periods of 10 minutes of treadmill running each at 30 m/minute with intervening 10 minute periods of rest. Hematoxylin-basic fuchsin-picric acid (HBFP) staining and plasma levels of cardiac troponin I (cTnI) were used to evaluate the ischemia-hypoxia injury in rat myocardium. Alteration levels in several autophagy proteins in the left ventricular myocardium were analyzed by Western blot. The phasic alterations of autophagy levels during EP-initiated cardioprotective phase were also examined.Compared with group C, the ischemia-hypoxia positive areas and IOD value in HBFP-staining and cTnI plasma levels increased significantly in group EE. Compared with group EE, the ischemia-hypoxia injury was markedly attenuated in group EP + EE. Compared with group C, the LC3-II/LC3-I ratio, a marker of autophagosome formation, was reduced in group EE, but the LC3-II/LC3-I ratio remained unaltered in group EP + EE. Furthermore, the LC3-II/LC3-I ratio increased significantly at 2 hours during the cardioprotective phase after EP.These results suggest that the activated autophagy level during the EP-initiated cardioprotective phase may be partly involved in the cardioprotective effects by maintaining a normal autophagy basal level during the subsequent exhaustive exercise in rat myocardium.

Late Exercise Preconditioning Promotes Autophagy against Exhaustive Exercise-Induced Myocardial Injury through the Activation of the AMPK-mTOR-ULK1 Pathway.

Accumulating evidence shows that the AMPK-mTOR pathway modulates autophagy via coordinated phosphorylation of ULK1. The aim of the present study was to investigate the relationship between AMPK, mTOR, and ULK1 during late exercise preconditioning (LEP), and to explore whether LEP-induced myocardial protection is related to the autophagy. The exercise preconditioning (EP) protocol was as follows: rats were instructed to for run four repeated in duration of 10 minutes (including 10 minutes rest between each period) on a treadmill. Exhaustive exercise (EE) after LEP pretreatment and administration of wortmannin (an autophagy inhibitor that suppresses Class III PI3K-kinase (PI3KC3) activity) were added to test the protective effect. Cardiac troponin I (cTnI), and transmission electron microscopy (TEM), along with hematoxylin-basic fuchsin-picric acid (HBFP) staining, were used to evaluate the myocardial ischemic-hypoxic injury and protection. Western blot was used to analyze the relationship of autophagy-associated proteins. Exhaustive exercise caused severe myocardial ischemic-hypoxic injury, which led to an increase in cTnI levels, changes of ischemia-hypoxia, and cells ultrastructure. Compared with the EE group, LEP significantly suppressed exhaustive exercise-induced myocardial injury. However, wortmannin attenuated LEP-induced myocardial protection by inhibiting autophagy. Compared with the C group, AMPK was increased in the LEP, EE, and LEP+EE groups, but phosphorylation of AMPK at Thr172 was not significantly changed. Exercise did not have any effect on mTOR expression. Compared with the C group, ULK1 was increased and the ULK1ser757/ULK1 ratio was decreased in the LEP and LEP+EE groups. ULK1 was not significantly affected in the EE group, however, phosphorylation of ULK1 at Ser757 was remarkably decreased. To sum up, our results suggested that LEP promoted autophagy through the activation of AMPK-mTOR-ULK1 pathway, and that activated autophagy was partially involved in myocardial protection against EE-induced myocardial ischemic-hypoxic injury.

Alterations of Cardiac KATP Channels and Autophagy Contribute in the Late Cardioprotective Phase of Exercise Preconditioning.

The cardiac effects of exercise preconditioning (EP) are well established; however, the mechanisms involving cardiac ATP-sensitive potassium channel (KATP channel) subunits and autophagy are yet to be fully established. The present work aims to investigate the alterations of cardiac KATP channel subunits Kir6.2, SUR2A, and autophagy-related LC3 during the late cardioprotective phase of EP against exhaustive exercise-induced myocardial injury. Rats run on treadmill for four running time intervals, each with 10 minutes running and rest. Exhaustive exercise was performed 24 h after EP. Cardiac biomarkers, cTnI and NT-proBNP, along with the histological stain, were served as indicators of myocardial injury. Cardiac KATP channel subunits Kir6.2 and SUR2A were analyzed in this study, and autophagy was evaluated by LC3. The results revealed that EP reduced the exhaustive exercise-induced high level of serum cTnI and myocardial ischemia/hypoxia; however, it did not reveal any changes in the serum NT-proBNP level or cardiac BNP. Cardiac SUR2A mRNA significantly upregulated during the exhaustive exercise. The high levels of Kir6.2, SUR2A, LC3IIpuncta and LC3II turnover observed after exhaustive exercise were significantly mitigated by EP in the late phase. These results suggest that EP alleviates myocardial injury induced by exhaustive exercise through the downregulation of cardiac KATP channels and autophagy.

H2O2 Signaling-Triggered PI3K Mediates Mitochondrial Protection to Participate in Early Cardioprotection by Exercise Preconditioning.

Previous studies have shown that early exercise preconditioning (EEP) imparts a protective effect on acute cardiovascular stress. However, how mitophagy participates in exercise preconditioning- (EP-) induced cardioprotection remains unclear. EEP may involve mitochondrial protection, which presumably crosstalks with predominant H2O2 oxidative stress. Our EEP protocol involves four periods of 10 min running with 10 min recovery intervals. We added a period of exhaustive running and a pretreatment using phosphoinositide 3-kinase (PI3K)/autophagy inhibitor wortmannin to test this protective effect. By using transmission electron microscopy (TEM), laser scanning confocal microscopy, and other molecular biotechnology methods, we detected related markers and specifically analyzed the relationship between mitophagic proteins and mitochondrial translocation. We determined that exhaustive exercise associated with various elevated injuries targeted the myocardium, oxidative stress, hypoxia-ischemia, and mitochondrial ultrastructure. However, exhaustion induced limited mitochondrial protection through a H2O2-independent manner to inhibit voltage-dependent anion channel isoform 1 (VDAC1) instead of mitophagy. EEP was apparently safe to the heart. In EEP-induced cardioprotection, EEP provided suppression to exhaustive exercise (EE) injuries by translocating Bnip3 to the mitochondria by recruiting the autophagosome protein LC3 to induce mitophagy, which is potentially triggered by H2O2 and influenced by Beclin1-dependent autophagy. Pretreatment with the wortmannin further attenuated these effects induced by EEP and resulted in the expression of proapoptotic phenotypes such as oxidative injury, elevated Beclin1/Bcl-2 ratio, cytochrome c leakage, mitochondrial dynamin-1-like protein (Drp-1) expression, and VDAC1 dephosphorylation. These observations suggest that H2O2 generation regulates mitochondrial protection in EEP-induced cardioprotection.

Parkin Mediates Mitophagy to Participate in Cardioprotection Induced by Late Exercise Preconditioning but Bnip3 Does Not.

BACKGROUND: Late exercise preconditioning (LEP) is confirmed to have a protective effect on acute cardiovascular stress. However, the mechanisms by which mitophagy participates in exercise preconditioning (EP)-induced cardioprotection remain unclear. LEP may involve mitophagy mediated by the receptors PARK2 gene-encoded E3 ubiquitin ligase (Parkin) and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3) to scavenge damaged mitochondria. METHODS: Our EP protocol involved four 10-minute periods of running, separated by 10-minute recovery intervals, plus a period of exhaustive running at 24 hours after EP. We assessed this late protective effect by injection of the autophagy inhibitor wortmannin, transmission electron microscopy, laser scanning confocal microscopy, and other molecular biotechnology methods; we simultaneously detected related markers, analyzed the specific relationships between mitophagy proteins, and assessed mitochondrial translocation. RESULTS: Exhaustive exercise (EE) causes serious injuries to cardiomyofibrils, inducing hypoxia-ischemia and changing the ultrastructure. EE fails to clear excessively generated mitochondria to link with LC3 accumulation. After EP, increased autophagy levels at 30 minutes were converted to mitophagy within 24 hours. We found that LEP significantly suppressed EE-induced injuries, which we confirmed by observing decreased levels of the mitochondria-localized proteins COX4/1 and TOM20. LEP to exhaustion caused mitochondrial degradation by increasing the efficiency of LC3-outer mitochondrial membrane translocation in a Parkin-mediated manner, in which activated protein kinase and TOM70 may play both key roles. However, we did not observe mitophagy to be associated with Bnip3 mediation in LEP-induced cardioprotection. However, Bnip3 may play a role in inducing mitochondrial LC3-II increases. Wortmannin had no effect on LC3 translocation; instead, it influenced LC3-I to convert to LC3-II. Thus, suppressing mitophagy led to the attenuation of EP-induced cardioprotection.

Cardioprotection of exercise preconditioning involving heat shock protein 70 and concurrent autophagy: a potential chaperone-assisted selective macroautophagy effect.

It has been confirmed that exercise preconditioning (EP) has a protective effect on acute cardiovascular stress. However, how Hsp70 participates in EP-induced cardioprotection is unknown. EP may involve Hsp70 to repair unfolded proteins or may also stabilize the function of the endoplasmic reticulum via Hsp70-related autophagy to work on a protective formation. Our EP protocol involves four periods of 10 min running with 10 min recovery intervals. We added a period of exhaustive running to test this protective effect, using histology and molecular biotechnology methods to detect related markers. EP provided cardioprotection at its early and late phases against exhaustive exercise-induced ischemic myocardial injury. Results showed that Hsp70 co-chaperone protein BAG3, ubiquitin adaptor p62 and critical autophagy protein LC3 were significantly upregulated at the early phase. Meanwhile, Hsp70, Hsp70/BAG3 co-localization extent, LC31 and LC3II were significantly upregulated at the late phase. Hsp70 mRNA levels and LC3II/I ratios were also consistent with the extent of myocardial injury following exhaustive exercise. Hsp70 increase was delayed relative to BAG3 and p62 after EP, indicating a pre-synthesized phenomenon of BAG3 and p62 for chaperone-assisted selective autophagy (CASA). The decreased Hsp70, BAG3 and p62 levels and increased Hsp70/BAG3 co-localization extent and LC3 levels induced by exhaustive exercise after EP suggest that EP-induced cardioprotection might associate with CASA. Hsp70 has a cardioprotective role and has a closer link with CASA in LEP. Additionally, EP may not cause exhaustion-dependent excessive autophagy regulation. Collectively, during early and late EP, CASA potentially plays different roles in cardioprotection.

Elevated C-type natriuretic peptide elicits exercise preconditioning-induced cardioprotection against myocardial injury probably via the up-regulation of NPR-B.

To evaluate exercise preconditioning (EP)-induced cardioprotective effects against exercise-induced acute myocardial injury and investigate the alterations of C-type natriuretic peptide (CNP) and its specific receptor, natriuretic peptide receptor B (NPR-B), during EP-induced cardioprotection. Rats were subjected to treadmill exercise as an EP model (4 periods of 10 min each at 30 m/min with intervening periods of rest lasting 10 min). High-intensity exercise was performed 0.5 and 24 h after the EP. EP attenuated high-intensity exercise-induced myocardial injury in both the early and late phases. After EP and high-intensity exercise, CNP and NPR-B levels increased robustly, but no alterations in the plasma CNP were observed. The enhanced NPR-B, plasma and tissue CNP, and its mRNA levels after high-intensity exercise were significantly elevated by EP. These results suggest that cardiac CNP and NPR-B play an important role in EP-mediated cardioprotection against high-intensity exercise-induced myocardial injury in rats.

Exercise preconditioning-induced late phase of cardioprotection against exhaustive exercise: possible role of protein kinase C delta.

The objective of this study was to investigate the late cardiac effect of exercise preconditioning (EP) on the exhaustive exercise-induced myocardial injury in rats and the role of protein kinase C (PKC) in EP. Rats were subjected to a run on the treadmill for four periods of 10 min each at 30 m/min with intervening periods of rest of 10 min as an EP protocol. The exhaustive exercise was performed 24 h after EP. PKC inhibitor chelerythrine (CHE) was injected before EP. The results showed that EP increased the running ability of rats, and alleviated the exhaustive exercise-induced injury in cardiomyocytes, but pretreatment with PKC inhibitor CHE did not abolish the late phase cardioprotection of EP. A significant increase of PKCδ, both at the protein level and the mRNA level in the left ventricular myocardium of rats, accompanied by its activated form (phosphorylated on Thr507, p-PKCδThr507) translocated to intercalated disks and was found in the late phase of EP. This circumstance was not attenuated by CHE. These results suggested that a high level of PKCδ might be involved in cardioprotection against myocardial damage, but if activated PKCδ at reperfusion took on a key role in cardioprotection was still an outstanding question.

Exercise preconditioning-induced early and late phase of cardioprotection is associated with protein kinase C epsilon translocation.

BACKGROUND: Exercise preconditioning (EP) can provide powerful protection to the heart. Evidence supports the contention that EP directly enhances myocardial tolerance to ischaemia through a protein kinase C (PKC)-mediated mechanism. However, studies investigating the role of isoform-specific PKC after EP are lacking. METHODS AND RESULTS: In this study, a male Sprague-Dawley rat model of EP was established (4 periods of 30 m/min for 10 min exercise then a 10 min rest at 0% grade treadmill exercise). Rats were subjected to exhaustive exercise to induce myocardial injury. Chelerythrine (5 mg/kg) was injected before EP to investigate the role of PKC in EP. EP was found to attenuate exhaustive exercise-induced myocardial injury in both of EP's 2 protective phases, especially the latter phase. After EP, PKCε was markedly upregulated, and PKCε was translocated to myocardial intercalated disks, and p-PKCε(Ser729) was translocated to the myocardial cytomembrane. Even though PKCε was markedly upregulated and translocated to intercalated disks during exhaustive exercise, p-PKCε(Ser729) was mainly distributed in the cytoplasm. A chelerythrine injection before EP did not suppress the activation of PKC and the protection of EP. CONCLUSIONS: These results indicate that PKCε plays an important role in EP-mediated protection of the myocardium during exhaustive exercise-induced myocardial injury, and that a chelerythrine injection during exercise is not suitable for demonstrating the role of PKCε.

Role of calcitonin gene-related peptide in cardioprotection of short-term and long-term exercise preconditioning.

PURPOSE: To examine the role of calcitonin gene-related peptide (CGRP) in cardioprotection of short-term and long-term exercise preconditioning (EP). METHODS: Male Sprague-Dawley rats were, respectively, subjected to continuous intermittent treadmill training 3 days or 3 weeks as short-term or long-term EP protocols. The myocardial injury induced by isoproterenol (ISO) was performed 24 hours after short-term and long-term EP. The myocardial injury was evaluated in terms of the serum cardiac troponin levels and the hematoxylin-basic fuchsin-picric acid staining. Additionally, serum CGRP levels, CGRP expression in the dorsal root ganglion (DRG), and heart were analyzed as possible mechanisms to explain short-term and long-term EP-induced cardioprotection. RESULTS: Both short-term and long-term EP markedly attenuated the isoproterenol-induced myocardial ischemia with lower serum cardiac troponin levels. Short-term EP does not alter serum CGRP levels and CGRP expression in the DRG and heart. Long-term EP significantly increases serum CGRP levels and CGRP expression in the DRG and heart. CONCLUSIONS: The results indicate that short-term EP does not increase the synthesis and release of CGRP. Therefore, the cardioprotective effect of short-term EP does not involve CGRP adaptation. Furthermore, long-term EP increases CGRP synthesis in the DRG and promotes CGRP release in the blood and heart. Hence, CGRP may play an important role in the cardioprotective effect of long-term EP.

Exercise preconditioning provides early cardioprotection against exhaustive exercise in rats: potential involvement of protein kinase C delta translocation.

The objective of this study was to investigate the early cardioprotective effect of exercise preconditioning (EP) on the exhaustive exercise-induced myocardial injury in rats and the role of protein kinase C delta isoform (PKCδ) in EP. Rats were subjected to run on the treadmill for four periods of 10 min each at 30 m/min with intervening periods of rest of 10 min as an EP protocol. The exhaustive exercise was performed 0.5 h after EP. PKC inhibitor chelerythrine (CHE) was injected before EP. Our results showed that EP markedly attenuated the exhaustive exercise-induced myocardial ischemia/hypoxia, ultrastructural damage, high serum cTnI, and NT-proBNP levels. CHE injection before EP did not abolish the protection of EP. Both exhaustive exercise and EP produced a significant increase in PKCδ and p-PKCδ(Thr507) protein levels in cardiomyocytes. However, the immunostaining of p-PKCδ(Thr507) in EP cardiomyocytes was primarily localized to intercalated disks and nuclei while the exhaustive exercise-induced high level p-PKCδ(Thr507) was mainly distributed in the cytoplasm. Moreover, the high PKCδ and p-PKCδ(Thr507) levels in exhaustive exercise were significantly down-regulated by EP. CHE did not attenuate the expressions of PKCδ and p-PKCδ(Thr507). These results indicate that an appropriate activation and translocation of PKCδ may represent a mechanism whereby EP can exert an early cardioprotection against exhaustive exercise-induced myocardial injury.