The effect of ischemic preconditioning on physical fitness and performance: a meta-analysis in healthy adults.

PURPOSE: This meta-analysis aims to assess the impact of ischemic preconditioning (IPC) on physical fitness and performance, with a focus on its specific role in aerobic endurance, anaerobic endurance, explosive power and strength. METHODS: Systematic searches were conducted across multiple databases (CNKI, CBM, Cochrane Library, Web of Science, PubMed, and Embase) up to September 6, 2023. We included studies that employed randomized controlled trial methods and sham ischemic preconditioning as the placebo group, and two reviewers independently screened literature and extracted data, using Review Manager 5.3 for analysis. RESULTS: This meta-analysis comprises 27 articles with 405 individuals, selected according to specified criteria. IPC significantly increased the blood lactate concentration after anaerobic speed endurance exercise (MD = 0.74, P = 0.03), the blood lactate concentration after incremental exercise (MD = 0.49, P = 0.04), the blood lactate concentration after muscular endurance exercise (MD = 0.68, P = 0.02), and the one-repetition maximum (MD = 1.38, P = 0.00001). Furthermore, it also significantly shortened completion time of the exercises primarily powered by glycolysis (MD = - 0.49, P = 0.01) and completion time of the exercises primarily powered by aerobic system (MD = - 7.27, P = 0.05), while marginally prolonging time to exhaustion (MD = 22.68, P = 0.08). However, IPC had no significant effect on maximum oxygen uptake, blood lactate concentration in fixed-load aerobic endurance exercise, peak power, or peak aerobic power, nor on completion time of the exercises primarily powered by phosphagen system. CONCLUSION: IPC could serve as a method to enhance physical performance, particularly for exercises primarily powered by aerobic system and glycolysis. Future research might explore how various cycles, locations, and widths of IPC affect the physical performance of participants with different activity levels.

Evaluation of Two Levels of Trace Mineral Supplementation to Beef Calves Prior to Weaning.

In this 2-year study, approximately 84 days prior to weaning, 24 calves/year (Angus × Hereford) were randomly assigned to one of two treatments: trace mineral (Cu, Se, and Zn) supplementation following NASEM (2016) recommendations (Control) or trace mineral supplementation above NASEM (2016) recommendations (Super). Calves were individually fed, and trace minerals were provided in 0.5 kg of dry distiller's grains three times weekly. Body weight (BW), blood, and liver samples were collected on d 0 and at weaning (d 84). Additional BW and blood samples were collected post-weaning on d 85, 87, 88, 91, 95, and 99 during the preconditioning phase. Initial liver concentrations of Se, Cu, and Zn were similar between treatments (p ≥ 0.69). At weaning, a year effect (p < 0.001) and a tendency for treatment × year effect (p = 0.09) were observed for Cu liver concentration. In year 2, but not in year 1, calves assigned to the Super treatment tended to have greater liver Cu concentration than calves assigned to the Control treatment. Except for Cu, a notoriously limited trace mineral in multiple geographical locations, the supplementation of trace minerals above the NASEM (2016) recommendations did not improve the mineral status of calves in this environment.

Exercise preconditioning mitigates brain injury after cerebral ischemia-reperfusion injury in rats by restraining TIMP1.

BACKGROUND: Cerebral ischemic disease is a common cerebrovascular disease, especially ischemic stroke. Exercise has protective functions on brain tissues following cerebral ischemia-reperfusion injury (CIRI), but its preventive effects and mechanisms in CIRI remain unclear. We aimed to investigate the effects and mechanisms of exercise preconditioning on CIRI. METHODS: The middle cerebral artery occlusion (MCAO) operation was prepared to establish CIRI rats. All rats were randomized into the MCAO, exercise (exercise preconditioning plus MCAO operation), vector (exercise preconditioning, MCAO operation plus intraventricular injection of empty vector), and tissue inhibitor of metalloprotease 1 overexpression (OE-TIMP1, exercise preconditioning, MCAO operation plus intraventricular injection of OE-TIMP1) groups. RESULTS: The results indicated that exercise preconditioning suppressed approximately 66.67% of neurological deficit scores and 73.79% of TIMP1 mRNA expression in MCAO rats, which were partially offset by OE-TIMP1. The protective effects of exercise against neuron death status and cerebral infarction size in MCAO rats were reversed by OE-TIMP1. It also confirmed that exercise weakened apoptosis and oxidative stress damage, with notable increases of B-cell lymphoma-2, superoxide dismutase, and glutathione peroxidase production, and evident decreases of BCL2-associated X, caspase 3, and malondialdehyde in MCAO rats, while these effects were partially reversed by OE-TIMP1. Additionally, the inhibitory effects of exercise on the protein levels of TIMP1, hypoxia-inducible factor-alpha, vascular endothelial growth factor receptor 2, vascular endothelial growth factor, and neurogenic locus notch homolog protein 1 in MCAO rats were partially reversed by OE-TIMP1. CONCLUSION: Altogether, exercise preconditioning had protective effects on CIRI by restraining TIMP1, which provided new therapeutic strategies for preventing CIRI.

Non-invasive remote ischemic preconditioning for patients with heart failure undergoing cardiac catheterization: a network meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to evaluate the efficacy of six non-invasive remote ischemic preconditioning (RIPC) interventions during the nursing care of patients with heart failure (HF) prior to cardiac catheterization. METHODS: A comprehensive search of nine Chinese and English online databases was conducted from the date of their inception to June 2023 to identify randomized controlled trials (RCTs) investigating RIPC in patients with HF prior to cardiac catheterization. Two independent investigators screened the articles, extracted data, and assessed their quality. The risk of bias was evaluated using the Cochrane risk-of-bias tool, and a network meta-analysis was conducted using R software. RESULTS: Four trials involving 511 patients with a low risk of bias were included in the analysis. Six non-invasive RIPC interventions were identified, all demonstrating effectiveness in reducing the incidence of contrast-induced acute kidney injury (CI-AKI). Among these, Intervention F (applying up to 50 mmHg above the resting systolic pressure for 5 min to the dominant leg or upper limb, repeated three times with an 18-minute interval) was deemed optimal, although the timing of the procedure was not specified. Intervention D (applying up to 200 mmHg pressure to the upper limb for 5 min, repeated four times with 5-minute intervals, within 45 min prior to cardiac catheterization, ) was considered suboptimal. CONCLUSION: Although Intervention D was recommended as the preferred option, none of the four trials examined its impact on the cardiac function of patients with HF. Large-scale, multi-center RCTs are required, with outcome indicators including cardiac function and the occurrence of CI-AKI, to better understand the therapeutic effects of RIPC on HF and reduce the incidence of CI-AKI. This will provide a more robust foundation for clinical practice.

[Electroacupuncture preconditioning prevents urticaria by regulating inflammatory response in rats with urticaria]. / é¢„ç”µé’ˆæ­¢ç—’ç©´å¯¹è°ƒèŠ‚ç‚Žæ€§ååº”é˜²æ²»è¨éº»ç–¹çš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of electroacupuncture (EA) preconditioning at "Quchi" (LI11) and "Xuehai" (SP10) in prevention of urticaria. METHODS: Twenty-four male SD rats were randomly divided into control, model and preconditioning of EA (Pre-EA) groups (8 rats/group). The urticaria model was established by intradermal injection of dilute allogeneic antioalbumin serum at the spots of the bilateral symmetry of the spine on the back, and followed by tail venous injection of mixture solution of egg albumin diluent, plus 0.5% Evans blue and normal saline. Ten days before the end of modeling, rats of the pre-EA group received EA stimulation of LI11 and SP10 for 20 min, once a day for 10 consecutive days. The times of rat's scratching the sensitized skin were recorded. HE staining method was used to observe the pathological changes of skin tissue, and toluidine blue staining method was used to observe the morphology of mast cells (MCs) in the skin, blood, mesentery, and peritoneal fluid, and calculate the degranulation rate. Immunohistochemical stainning was used to detect immunoglobulin E (IgE), histamine (HIS), and 5-hydroxytryptamine (5-HT) expressions in subcutaneous tissue. NOD like receptor thermal domain associated protein 3 (NLRP3) inflammasome, apoptosis related granule protein (ASC), and cysteine aspartate aminotransferase 1 (Caspase-1) protein expression levels in skin tissue were detected by Western blot. The contents of serum interleukin(IL)-1ß and IL-18 were detected using ELISA method. RESULTS: Compared with the control group, the scratching times, amount of Evans blue exudation of the sensitized blue spots, degranulation rate of MCs in skin, blood, mesentery and peritoneal fluid, the expression levels of IgE, HIS, 5-HT in subcutaneous tissue, protein expression levels of NLRP3, ASC, Caspase-1 in skin tissue, and the contents of serum IL-1ß and IL-18 were significantly increased (P<0.01, P<0.05) in the model group. In comparison with the model group, the scratching times, amount of Evans blue exudation of the sensitized blue spots, degranulation rate of MCs, the expression levels of IgE, HIS, 5-HT in subcutaneous tissue, protein expression levels of NLRP3, ASC, Caspase-1 in skin tissue, and the contents of serum IL-1ß and IL-18 in EA group were significantly decreased (P<0.01, P<0.05). CONCLUSIONS: EA preconditioning at LI11 and SP10 can prevent and treat UR by inhibiting inflammatory response, which is related to the regulation of pyroptosis.

The Impact of Remote Ischemic Preconditioning on Inflammation Markers in Patients Undergoing Coronary Artery Bypass Grafting.

Background: This study aimed to investigate if remote ischemic preconditioning reduces the inflammatory process on patients undergoing coronary artery bypass grafting (CABG). Methods: We conducted a case-control study involving 80 patients, half of whom underwent ischemic preconditioning for severe coronary artery disease (CAD) and subsequently underwent CABG. We assessed interleukin (IL)-1 and IL-6 levels using the enzyme-linked immunosorbent assay (ELISA) method, high-sensitivity troponin I (hsTnI) using chemiluminescent immunoassay (CLIA), and C-reactive protein (CRP) using the turbidimetric method at three key time points: before surgery (visit 1 or V1), immediately postoperatively (visit 2 or V2), and 1 week postoperatively (visit 3 or V3) in all subjects. Results: Ischemic preconditioned patients showed a significant decrease in proinflammatory markers (IL-1, IL-6) but not in CRP or hsTnI. Conclusions: This study demonstrated that remote ischemic preconditioning significantly reduced the levels of specific proinflammatory markers (IL-1 and IL-6), which may suggest general systemic protection. However, it did not demonstrate cardioprotection per se, as evidenced by the absence of a statistically significant decrease in hsTnI level.

Metabolic characteristics of ischaemic preconditioning induced performance improvement in Taekwondo athletes using LC‒MS/MS-based plasma metabolomics.

In recent years, ischemic preconditioning (IPC) has garnered significant attention in sports research. While IPC has demonstrated positive effects in high-intensity sports such as judo and swimming, its potential benefits for enhancing the performance of Taekwondo athletes have not been extensively studied. This study aimed to investigate the effects of IPC on taekwondo performance and to observe the metabolic characteristics associated with enhancing sports performance via LC‒MS/MS-based plasma metabolomics. Seventeen participants underwent the repeated frequency speed of kick test (FSKT) after IPC, along with pre- and post-exercise plasma metabolite analysis. Differential abundance metabolite analysis, enriched pathway analysis, and weighted gene coexpression network analysis (WGNCA) were employed to delve into metabolic characteristics. The findings highlighted a significant enhancement in FSKT performance in the experimental group. Metabolomic analysis revealed 109 differentially abundant metabolites, including Dl-lactate, hypoxanthine, acetylcarnitine, and acetylsalicylic acid. Enriched pathway analysis revealed pathways such as pentose and glucuronic acid interconversion, ascorbic acid and aldonic acid metabolism, the pentose phosphate pathway (PPP), and the Warburg effect. In conclusion, IPC can significantly increase the specific athletic abilities of Taekwondo athletes, with enhancements linked to anaerobic metabolism, PPP utilization, the Warburg effect for energy production, redox system stability, reduced muscle fatigue, and pain alleviation.

The IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): multicenter pig study on the effect of ischemic preconditioning.

Numerous cardioprotective interventions have been reported to reduce myocardial infarct size (IS) in pre-clinical studies. However, their translation for the benefit of patients with acute myocardial infarction (AMI) has been largely disappointing. One reason for the lack of translation is the lack of rigor and reproducibility in pre-clinical studies. To address this, we have established the European IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) pig AMI network with centralized randomization and blinded core laboratory IS analysis and validated the network with ischemic preconditioning (IPC) as a positive control. Ten sites in the COST Innovators Grant (IG16225) network participated in the IMPACT network. Three sites were excluded from the final analysis through quality control of infarct images and use of pre-defined exclusion criteria. Using a centrally generated randomization list, pigs were allocated to myocardial ischemia/reperfusion (I/R, N = 5/site) or IPC + I/R (N = 5/site). The primary endpoint was IS [% area-at-risk (AAR)], as quantified by triphenyl-tetrazolium-chloride (TTC) staining in a centralized, blinded core laboratory (5 sites), or IS [% left-ventricular mass (LV)], as quantified by a centralized, blinded cardiac magnetic resonance (CMR) core laboratory (2 sites). In pooled analyses, IPC significantly reduced IS when compared to I/R (57 ± 14 versus 32 ± 19 [%AAR] N = 25 pigs/group; p < 0.001; 25 ± 13 versus 14 ± 8 [%LV]; N = 10 pigs/group; p = 0.021). In site-specific analyses, in 4 of the 5 sites, IS was significantly reduced by IPC when compared to I/R when quantified by TTC and in 1 of 2 sites when quantified by CMR. A pig AMI multicenter European network with centralized randomization and core blinded IS analysis was established and validated with the aim to improve the reproducibility of cardioprotective interventions in pre-clinical studies and the translation of cardioprotection for patient benefit.

Toward understanding the brain tissue behavior due to preconditioning: an experimental study and RVE approach.

Brain tissue under preconditioning, as a complex issue, refers to repeated loading-unloading cycles applied in mechanical testing protocols. In previous studies, only the mechanical behavior of the tissue under preconditioning was investigated; However, the link between macrostructural mechanical behavior and microstructural changes in brain tissue remains underexplored. This study aims to bridge this gap by investigating bovine brain tissue responses both before and after preconditioning. We employed a dual approach: experimental mechanical testing and computational modeling. Experimental tests were conducted to observe microstructural changes in mechanical behavior due to preconditioning, with a focus on axonal damage. Concurrently, we developed multiscale models using statistically representative volume elements (RVE) to simulate the tissue's microstructural response. These RVEs, featuring randomly distributed axonal fibers within the extracellular matrix, provide a realistic depiction of the white matter microstructure. Our findings show that preconditioning induces significant changes in the mechanical properties of brain tissue and affects axonal integrity. The RVE models successfully captured localized stresses and facilitated the microscopic analysis of axonal injury mechanisms. These results underscore the importance of considering both macro and micro scales in understanding brain tissue behavior under mechanical loading. This comprehensive approach offers valuable insights into mechanotransduction processes and improves the analysis of microstructural phenomena in brain tissue.

Noisy nests: Early-life noise exposure impacts songbird fitness.

Recent findings indicate that noise pollution - presented in the absence of other variables - has both immediate-term impacts on young birds' developmental rates and physiology as well as long-term effects on adult telomere length and reproductive success. This work highlights yet another set of negative impacts caused by anthropogenic noise, and suggests that the dramatic fitness consequences observed likely have implications for the evolution of learning and behavior in animals living in noisy environments.

Acute ergogenic effects of repetitive maximal breath-holding maneuvers on hematological and physiological responses: a graded exercise test investigation.

PURPOSE: Repetitive maximal breath-holds (BHs or apneas) have been noted to induce advantageous hematological and blood buffering changes. Building on this, the hypothesis was formulated that the execution of repeated maximal BH efforts might lead to subsequent enhancements in performance during a time-to-exhaustion test. METHODS: This study investigated the acute effects of five static maximal breath-holding maneuvers conducted with face immersion in cold water (10 °C) on subsequent graded exercise test (GET) performance. Seventeen well-trained participants completed a GET on a motorized treadmill under two randomized cross-over conditions: baseline measurement (CON) and after five repeated maximal breath-holding efforts (EXP). RESULTS: The GET protocol consists of incremental increases in speed until exhaustion. After the fifth breath-hold, participants in the EXP condition exhibited significant (P < 0.05) increases in hematocrit, hemoglobin concentration, red blood cell count, and muscle deoxygenation, accompanied by a reduction in blood lactate concentration (4.09 ± 2.21%, 3.9 ± 1.76%, 3.96 ± 2.1%, 81.48 ± 23.83%, and 15.22 ± 17.64%, respectively), compared to CON. During GET, the EXP condition showed a significantly (P < 0.05) delayed onset time of the second ventilatory threshold (3.14 ± 5.85%) and (P < 0.05) increased time to exhaustion (0.75 ± 1.02%). CONCLUSION: This evidence suggests that repeated maximal static breath-holding maneuvers enhance the oxygen delivery system by increasing the circulation of reserve red blood cells, heightened muscle oxygen deoxygenation, enhanced aerobic metabolism utilization, and postponing the transition from aerobic to anaerobic metabolism, implying a potential ergogenic effect. While pre-exercise breath-holding shows promise for improving time-to-exhaustion and optimizing subsequent distance running performance, further in-depth investigation is essential to fully elucidate the underlying mechanistic factors.

Aerobic interval training preconditioning protocols inhibit isoproterenol-induced pathological cardiac remodeling in rats: Implications on oxidative balance, autophagy, and apoptosis.

This study aimed to investigate the potential cardioprotective effects of moderate and high-intensity aerobic interval training (MIIT and HIIT) preconditioning. The focus was on histological changes, pro-oxidant-antioxidant balance, autophagy initiation, and apoptosis in myocardial tissue incited by isoproterenol-induced pathological cardiac remodeling (ISO-induced PCR). Male Wistar rats were randomly divided into control (n â€‹= â€‹6), ISO (n â€‹= â€‹8), MIIT (n â€‹= â€‹4), HIIT (n â€‹= â€‹4), MIIT â€‹+ â€‹ISO (n â€‹= â€‹8), and HIIT â€‹+ â€‹ISO (n â€‹= â€‹8) groups. The MIIT and HIIT protocols were administered for 10 weeks, followed by the induction of cardiac remodeling using subcutaneous injection of ISO (100 â€‹mg/kg for two consecutive days). Alterations in heart rate (HR), mean arterial pressure (MAP), rate pressure product (RPP), myocardial oxygen consumption (M V ˙ O2), cardiac hypertrophy, histopathological changes, pro-oxidant-antioxidant balance, autophagy biomarkers (Beclin-1, Atg7, p62, LC3 I/II), and apoptotic cell distribution were measured. The findings revealed that the MIIT â€‹+ â€‹ISO and HIIT â€‹+ â€‹ISO groups demonstrated diminished myocardial damage, hemorrhage, immune cell infiltration, edema, necrosis, and apoptosis compared to ISO-induced rats. MIIT and HIIT preconditioning mitigated HR, enhanced MAP, and preserved M V ˙ O2 and RPP. The pro-oxidant-antioxidant balance was sustained in both MIIT â€‹+ â€‹ISO and HIIT â€‹+ â€‹ISO groups, with MIIT primarily inhibiting pro-apoptotic autophagy progression through maintaining pro-oxidant-antioxidant balance, and HIIT promoting pro-survival autophagy. The results demonstrated the beneficial effects of both MIIT and HIIT as AITs preconditioning in ameliorating ISO-induced PCR by improving exercise capacity, hemodynamic parameters, and histopathological changes. Some of these protective effects can be attributed to the modulation of cardiac apoptosis, autophagy, and oxidative stress.

Influence of Anesthetic Regimes on Extracellular Vesicles following Remote Ischemic Preconditioning in Coronary Artery Disease.

Remote ischemic preconditioning (RIPC) reduces ischemia-reperfusion injury in aortocoronary bypass surgery, potentially via extracellular vesicles (EVs) and their micro-RNA content. Clinical data implicate that propofol might inhibit the cardioprotective RIPC effect. This prospective, randomized study investigated the influence of different anesthetic regimes on RIPC efficacy and EV micro-RNA signatures. We also assessed the impact of propofol on cell protection after hypoxic conditioning and EV-mediated RIPC in vitro. H9c2 rat cardiomyoblasts were subjected to hypoxia, with or without propofol, and subsequent simulated ischemia-reperfusion injury. Apoptosis was measured by flow cytometry. Blood samples of 64 patients receiving anesthetic maintenance with propofol or isoflurane, along with RIPC or sham procedures, were analyzed, and EVs were enriched using a polymer-based method. Propofol administration corresponded with increased Troponin T levels (4669 ± 435.6 pg/mL), suggesting an inhibition of the cardioprotective RIPC effect. RIPC leads to a notable rise in miR-21 concentrations in the group receiving propofol anesthesia (fold change 7.22 ± 6.6). In vitro experiments showed that apoptosis reduction was compromised with propofol and only occurred in an EV-enriched preconditioning medium, not in an EV-depleted medium. Our study could clinically and experimentally confirm propofol inhibition of RIPC protection. Increased miR-21 expression could provide evidence for a possible inhibitory mechanism.

Innovative Air-Preconditioning Method for Accurate Particulate Matter Sensing in Humid Environments.

Smart cities rely on a network of sensors to gather real-time data on various environmental factors, including air quality. This paper addresses the challenges of improving the accuracy of low-cost particulate matter sensors (LCPMSs) which can be compromised by environmental conditions, such as high humidity, which is common in many urban areas. Such weather conditions often lead to the overestimation of particle counts due to hygroscopic particle growth, resulting in a potential public concern, although most of the detected particles consist of just water. The paper presents an innovative design for an indicative air-quality measuring station that integrates the particulate matter sensor with a preconditioning subsystem designed to mitigate the impact of humidity. The preconditioning subsystem works by heating the incoming air, effectively reducing the relative humidity and preventing the hygroscopic growth of particles before they reach the sensor. To validate the effectiveness of this approach, parallel measurements were conducted using both preconditioned and non-preconditioned sensors over a period of 19 weeks. The data were analyzed to compare the performance of the sensors in terms of accuracy for PM1, PM2.5, and PM10 particles. The results demonstrated a significant improvement in measurement accuracy for the preconditioned sensor, especially in environments with high relative humidity. When the conditions were too severe and both sensors started measuring incorrect values, the preconditioned sensor-measured values were closer to the actual values. Also, the period of measuring incorrect values was shorter with the preconditioned sensor. The results suggest that the implementation of air preconditioning subsystems in LCPMSs deployed in smart cities can provide a cost-effective solution to overcome humidity-related inaccuracies, thereby improving the overall quality of measured air pollution data.

Alternation of gene expression in brain-derived exosomes after cerebral ischemic preconditioning in mice.

Aims: Cerebral ischemic preconditioning is a neuroprotective therapy against cerebral ischemia and ischemia-reperfusion injury. This study aims to demonstrate the alternation of gene expression in exosomes from brain tissue of mice after ischemic preconditioning and their potential functions. Methods: Ten mice were divided into the sham and the cerebral ischemic preconditioning groups. Their brain tissues were harvested, from which the exosomes were extracted. The characteristics and protective effects of exosomes were evaluated. Whole transcriptome sequencing was used to demonstrate the gene expression discrepancy between the exosomes from the two groups of mice brains. Volcano graphs and heatmaps were used to picture the difference in expression quantity of mRNA, lncRNA, and circRNA. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to demonstrate the functions of differentially expressed RNAs. Results: Exosomes were successfully extracted, and those from the cerebral ischemic preconditioning group had better protective effects on cells that received oxygen-glucose deprivation and restoration injury. A total of 306 mRNAs and 374 lncRNAs were significantly upregulated, and 320 mRNAs and 405 lncRNAs were significantly downregulated in the preconditioning group. No circRNAs were differentially expressed between the two groups. GO and KEGG pathway analysis indicated that the functions of differentially expressed RNAs were related to both neural protective and injurious effects. Conclusion: The brain-derived exosomes may participate in the neuroprotective effect of cerebral ischemic preconditioning. Thorough research is necessary to investigate exosome functions derived from the ischemic preconditioned brain.

Dimethyl Fumarate Preconditioning can Reinforce the Therapeutic Potential of Bone Marrow Mesenchymal Stem Cells through Trophic Factor Profile Enhancement.

Background: Numerous studies have confirmed the therapeutic efficacy of bone marrow-derived mesenchymal stem cells (BM-MSCs) in addressing neurologic disorders. To date, several preconditioning strategies have been designed to improve the therapeutic potential of these stem cells. This study was designed to evaluate the preconditioning effect of dimethyl fumarate (DMF) on the expression of main trophic factors in human BM-MSCs. Materials and Methods: Initially, the identity of stem cells was confirmed through the evaluation of surface markers and their capacity for osteogenic and adipogenic differentiation using flow cytometry and differentiation assay, respectively. Subsequently, stem cells were subjected to different concentrations of DMF for 72 hours and their viability was defined by MTT assay. Following 72-hour preconditioning period with 10 µM DMF, gene expression was assessed by quantitative RT-PCR. Results: Our findings demonstrated that the isolated stem cells expressed cardinal MSC surface markers and exhibited osteogenic and adipogenic differentiation potential. MTT results confirmed that 10 µM DMF was an optimal dose for maintaining cell viability. Preconditioning of stem cells with DMF significantly upregulated the expression of BDNF, NGF, and NT-3. Despite a slight increase in transcript level of GDNF and VEGF after DMF preconditioning, this difference was not statistically significant. Conclusions: Our findings suggest that DMF preconditioning can enhance the expression of major neurotrophic factors in human BM-MSCs. Given the curative potential of both BM-MSCs and DMF in various neurological disease models and preconditioning outcomes, their combined use may synergistically enhance their neuroprotective properties.

Ischemic-Preconditioning Induced Serum Exosomal miR-133a-3p Improved Post-Myocardial Infarction Repair via Targeting LTBP1 and PPP2CA.

Background: Ischemic preconditioning-induced serum exosomes (IPC-exo) protected rat heart against myocardial ischemia/reperfusion injury. However, whether IPC-exo regulate replacement fibrosis after myocardial infarction (MI) and the underlying mechanisms remain unclear. MicroRNAs (miRs) are important cargos of exosomes and play an essential role in cardioprotection. We aim to investigate whether IPC-exo regulate post-MI replacement fibrosis by transferring cardioprotective miRs and its action mechanism. Methods: Exosomes obtained from serum of adult rats in control (Con-exo) and IPC groups were identified and analyzed, subsequently intracardially injected into MI rats following ligation. Their miRs profiles were identified using high-throughput miR sequencing to identify target miRs for bioinformatics analysis. Luciferase reporter assays confirmed target genes of selected miRs. IPC-exo transfected with selected miRs antagomir or NC were intracardially administered to MI rats post-ligation. Cardiac function and degree of replacement fibrosis were detected 4 weeks post-MI. Results: IPC-exo exerted cardioprotective effects against excessive replacement fibrosis. MiR sequencing and RT-qPCR identified miR-133a-3p as most significantly different between IPC-exo and Con-exo. MiR-133a-3p directly targeted latent transforming growth factor beta binding protein 1 (LTBP1) and protein phosphatase 2, catalytic subunit, alpha isozyme (PPP2CA). KEGG analysis showed that transforming growth factor-ß (TGF-ß) was one of the most enriched signaling pathways with miR-133a-3p. Comparing to injection of IPC-exo transfected with miR-133a-3p antagomir NC, injecting IPC-exo transfected with miR-133a-3p antagomir abolished protective effects of IPC-exo on declining excessive replacement fibrosis and cardiac function enhancement, while increasing the messenger RNA and protein expression of LTBP1, PPP2CA, and TGF-ß1in MI rats. Conclusion: IPC-exo inhibit excessive replacement fibrosis and improve cardiac function post-MI by transferring miR-133a-3p, the mechanism is associated with directly targeting LTBP1 and PPP2CA, and indirectly regulating TGF-ß pathway in rats. Our finding provides potential therapeutic effect of IPC-induced exosomal miR-133a-3p for cardiac repair.

Cardioprotective microRNAs (protectomiRs) in a pig model of acute myocardial infarction and cardioprotection by ischaemic conditioning: MiR-450a.

BACKGROUND AND PURPOSE: Cardioprotective miRNAs (protectomiRs) are promising therapeutic tools. Here, we aimed to identify protectomiRs in a translational porcine model of acute myocardial infarction (AMI) and to validate their cardiocytoprotective effect. EXPERIMENTAL APPROACH: ProtectomiR candidates were selected after systematic analysis of miRNA expression changes in cardiac tissue samples from a closed-chest AMI model in pigs subjected to sham operation, AMI and ischaemic preconditioning, postconditioning or remote preconditioning, respectively. Cross-species orthologue protectomiR candidates were validated in simulated ischaemia-reperfusion injury (sI/R) model of isolated rat ocardiomyocytes and in human AC16 cells as well. For miR-450a, we performed target prediction and analysed the potential mechanisms of action by GO enrichment and KEGG pathway analysis. KEY RESULTS: Out of the 220 detected miRNAs, four were up-regulated and 10 were down-regulated due to all three conditionings versus AMI. MiR-450a and miR-451 mimics at 25 nM were protective in rat cardiomyocytes, and miR-450a showed protection in human cardiomyocytes as well. MiR-450a has 3987 predicted mRNA targets in pigs, 4279 in rats and 8328 in humans. Of these, 607 genes are expressed in all three species. A total of 421 common enriched GO terms were identified in all three species, whereas KEGG pathway analysis revealed 13 common pathways. CONCLUSION AND IMPLICATIONS: This is the first demonstration that miR-450a is associated with cardioprotection by ischaemic conditioning in a clinically relevant porcine model and shows cardiocytoprotective effect in human cardiomyocytes, making it a promising drug candidate. The mechanism of action of miR-450a involves multiple cardioprotective pathways.

Comment on, "Hypoxia preconditioning protects neuronal cells against traumatic brain injury through stimulation of glucose transport mediated by HIF-1α/GLUTs signaling pathway in rat".

Wu et al. (2021) investigated the neuroprotective effects of hypoxia preconditioning (HPC) in a rat model of traumatic brain injury (TBI). The study demonstrated that HPC enhances brain resilience to TBI by upregulating glucose transporters GLUT1 and GLUT3 through the HIF-1α signaling pathway. Comprehensive molecular and histological analyses confirmed increased expression of these transporters, correlating with reduced neuronal apoptosis and cerebral edema. The robust methodology, including rigorous statistical validation and time-course assessments, underscores HPC's potential therapeutic role in mitigating neuronal loss and improving glucose transport post-injury. However, the study could be strengthened by incorporating additional preconditioning controls, comparative analyses with other neuroprotective strategies, and exploring downstream metabolic effects in greater detail. Furthermore, expanding the research to include diverse animal models and examining sex-dependent responses would enhance the generalizability and translational relevance of the findings. Future studies should also integrate metabolic flux analysis and advanced imaging techniques to further elucidate HPC's mechanisms of action.