Simulated spaceflight-induced cardiac remodeling is modulated by gut microbial-derived trimethylamine N-oxide.

Spaceflight is physically demanding and can negatively affect astronauts' health. It has been shown that the human gut microbiota and cardiac function are affected by spaceflight and simulated spaceflight. This study investigated the effects of the gut microbiota on simulated spaceflight-induced cardiac remodeling using 10° of head-down bed rest (HDBR) in rhesus macaques and 30° of hindlimb unloading (HU) in mice. The gut microbiota, fecal metabolites, and cardiac remodeling were markedly affected by HDBR in macaques and HU in mice, cardiac remodeling in control mice was affected by the gut microbiota of HU mice and that of HU mice was protected by the gut microbiota of control mice, and there was a correlation between cardiac remodeling and the gut microbial-derived metabolite trimethylamine N-oxide. These findings suggest that spaceflight can affect cardiac remodeling by modulating the gut microbiota and fecal metabolites.

Simple and sensitive detection of miRNA-122 based on a micro-biosensor through square wave voltammetry.

The simple and sensitive detection of miRNA-122 in blood is crucially important for early hepatocellular carcinoma (HCC) diagnosis. In this work, a platinum microelectrode (PtµE) was prepared and electrodeposited with molybdenum disulfide (MoS2) and gold nanoparticles (AuNP), respectively, and denoted as PtµE/MoS2/Au. The prepared PtµE/MoS2/Au was used as the microsensor for the detection of miRNA-122 combined with the probe DNA as a biorecognition element which is the complementary strand of miRNA-122. The PtµE/MoS2/Au conjugated with the probe DNA modified with sulfydryl units was used as the micro-biosensor for the detection of miRNA-122. The square wave voltammetry was performed for the quantitative detection of miRNA-122 using [Fe(CN)6]4-/3- as a mediator. Under the optimized conditions, the PtµE/MoS2/Au micro-biosensor shows a linear detection toward miRNA-122 ranging from 10-11 to 10-8 M (S = 6.9 nA dec-1, R2 = 0.9997), and the detection limit is 1.6 × 10-12 M (3σ/b). The PtµE/MoS2/Au micro-biosensor demonstrates good selectivity against other types of proteins and small molecules, and has good reproducibility. Moreover, the PtµE/MoS2/Au micro-biosensor was successfully applied for the measurement of miRNA-122 in real blood samples. Herein, the proposed detection assay could be a potential tool in HCC clinical diagnostics with high sensitivity.

Development and validation of a nomogram for the early prediction of acute kidney injury in hospitalized COVID-19 patients.

Introduction: Acute kidney injury (AKI) is a prevalent complication of coronavirus disease 2019 (COVID-19) and is closely linked with a poorer prognosis. The aim of this study was to develop and validate an easy-to-use and accurate early prediction model for AKI in hospitalized COVID-19 patients. Methods: Data from 480 COVID-19-positive patients (336 in the training set and 144 in the validation set) were obtained from the public database of the Cancer Imaging Archive (TCIA). The least absolute shrinkage and selection operator (LASSO) regression method and multivariate logistic regression were used to screen potential predictive factors to construct the prediction nomogram. Receiver operating curves (ROC), calibration curves, as well as decision curve analysis (DCA) were adopted to assess the effectiveness of the nomogram. The prognostic value of the nomogram was also examined. Results: A predictive nomogram for AKI was developed based on arterial oxygen saturation, procalcitonin, C-reactive protein, glomerular filtration rate, and the history of coronary artery disease. In the training set, the nomogram produced an AUC of 0.831 (95% confidence interval [CI]: 0.774-0.889) with a sensitivity of 85.2% and a specificity of 69.9%. In the validation set, the nomogram produced an AUC of 0.810 (95% CI: 0.737-0.871) with a sensitivity of 77.4% and a specificity of 78.8%. The calibration curve shows that the nomogram exhibited excellent calibration and fit in both the training and validation sets. DCA suggested that the nomogram has promising clinical effectiveness. In addition, the median length of stay (m-LS) for patients in the high-risk group for AKI (risk score ≥ 0.122) was 14.0 days (95% CI: 11.3-16.7 days), which was significantly longer than 8.0 days (95% CI: 7.1-8.9 days) for patients in the low-risk group (risk score <0.122) (hazard ratio (HR): 1.98, 95% CI: 1.55-2.53, p < 0.001). Moreover, the mortality rate was also significantly higher in the high-risk group than that in the low-risk group (20.6 vs. 2.9%, odd ratio (OR):8.61, 95%CI: 3.45-21.52). Conclusions: The newly constructed nomogram model could accurately identify potential COVID-19 patients who may experience AKI during hospitalization at the very beginning of their admission and may be useful for informing clinical prognosis.

RuO2/rGO heterostructures as mimic peroxidases for colorimetric detection of glucose.

The successful synthesis of ruthenium oxide/reduced graphene oxide (RuO2/rGO) heterostructures by one-pot hydrothermal method using graphene oxides and RuCl3 as precursors is reported. The heterostructures had high peroxidase-like (POD-like) activities, which catalyzes the oxidation of classical peroxidase substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2 to create a blue colored reaction product. The catalytic activity was significantly enhanced by the synergistic effect between RuO2 nanoparticles and rGO. RuO2/rGO had a low Km of 0.068 mM and a high vmax of 1.228 × 10-7 M·s-1 towards TMB in the TMB-H2O2 catalytic oxidation system. In addition, the POD-like activity originating from the electron transfer mechanism was confirmed by cytochrome C (Cyt C) oxidation experiment. A colorimetric method based on RuO2/rGO heterostructures was developed with good sensitivity and selectivity for glucose detection with a limit of detection of 3.34 µM and a linear range of 0-1500 µM. The RuO2/rGO heterostructures have potential applications in the biomedical areas, such as biosensor and diagnostics.

Mental Health Among Medical Students During COVID-19: A Systematic Review and Meta-Analysis.

Background: The mental health of medical students is an issue worthy of attention, especially during COVID-19. Many studies have shown that depression and anxiety are the main problems faced by medical students. To assess the pooled prevalence of depression and anxiety among medical students worldwide, we conducted this meta-analysis. Methods: According to PRISMA, we used a computerized strategy to search studies in EMBASE, PubMed, PsycArticles, Web of Science, and China Biology Medicine disc. The pooled prevalence of depression and anxiety was calculated by a random-effects model. Heterogeneity was explored by subgroup analysis. Sensitivity analysis and publication bias were also carried out in this meta-analysis. Results: Of 1316 studies, 41 studies were selected based on 36608 medical students. The pooled depression prevalence was 37.9% (95% CI: 30.7-45.4%), and pooled anxiety prevalence was 33.7% (95% CI: 26.8-41.1%). The prevalence of depression and anxiety among medical students varied by gender, country, and continent. Conclusion: The data reported that the prevalence of depression and anxiety among medical students during COVID-19 was relatively higher than those of the general population and the healthcare workers. The impact of COVID-19 on medical students and how to protect the mental health of medical students are needed to determine through further research. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021274015], identifier [CRD42021274015].

Secondary channel estimation in spatial active noise control systems using a single moving higher order microphone.

Spatial active noise control (ANC) systems focus on minimizing unwanted acoustic noise over continuous spatial regions by generating anti-noise fields with secondary loudspeakers. Conventionally, error microphones are necessary inside the region to measure the channels from the secondary loudspeakers to the error microphones and record the residual sound field during the noise control. These error microphones highly limit the implementation of spatial ANC systems because of their impractical geometry and obstruction to the users from accessing the region. Recent advances, such as virtual sensing, focus on ANC with microphones placed away from the region. While these techniques relax the usage of error microphones during the noise control, an error microphone array remains necessary during the secondary channel estimation. In this paper, we propose a method to estimate secondary channels without using an error microphone array. Instead, a moving higher order microphone is applied to obtain the secondary channels from the secondary loudspeakers to the region of interest, which includes all desired error microphone locations. By simulation, we show that the proposed method is robust against various measuring errors introduced by the movement of the microphone and is suitable for the secondary channel estimation in spatial ANC systems.

The Effects of Sodium Propionate Supplementation in the Diet with High Soybean Meal on Growth Performance, Intestinal Health, and Immune Resistance to Bacterial Infection in Turbot (Scophthalmus maximus L.).

Short-chain fatty acids (SCFAs) are the products of the microbial fermentation of dietary fiber in the intestine. Acetate, propionate, and butyrate are the most abundant SCFA metabolites and play an important role in maintaining host health. This study was aimed at investigating the effects of sodium propionate (NaP) supplementation in the diet with a high proportion of soybean meal (SBM) on the growth, inflammatory status, and anti-infectious ability in juvenile turbot. Four experimental diets were designed: (1) fish meal- (FM-) based diet (control group), (2) SBM protein replacing 45% FM protein in the diet (high SBM group), (3) 0.5% NaP supplementation in the high SBM diet (high SBM+0.5% NaP group), and (4) 1.0% NaP supplementation in the high SBM diet (high SBM+1.0% NaP group). The results confirmed that the fish fed the high SBM diet for 8 weeks showed the decreased growth performance, the typical enteritis symptoms, and the increased mortality responding to Edwardsiella tarda (E. tarda) infection. However, 0.5% NaP supplementation in the high SBM diet promoted the growth performance of turbot and restored the activities of digestive enzymes in the intestine. Moreover, dietary NaP ameliorated the intestinal morphology, enhanced the expression of intestinal tight junction proteins, improved the antioxidant capacity, and suppressed the inflammatory status in turbot. Finally, the expression of antibacterial components and the resistance to bacterial infection were increased in NaP-fed turbot, especially in high SBM+1.0% NaP group. In conclusion, the supplementation of NaP in high SBM diet promotes the growth and health in turbot and provides a theoretical basis for the development of NaP as a functional additive in fish feed.

Systematic review and meta-analysis: gray-scale ultrasound and shear wave elastography in the diagnosis of primipara pregnancy and delivery.

BACKGROUND: The combination of shear wave elastography (SWE) and gray-scale ultrasound is widely used in the measurement of female pelvic floor muscle. However, the value of gray-scale ultrasound combined with SWE in the evaluation of primipara pregnancy and delivery is still controversial. METHODS: Using the PubMed, Web of Science, Spring and Science Direct databases, clinical studies on gray-scale ultrasound combined with SWE on the diagnosis of primiparous pregnancy and childbirth published from January 2010 to December 2020 were searched. The RevMan5.3 software was used to conduct a meta-analysis of the indicators of gray-scale ultrasound combined with SWE for primiparas and non-primiparas, including: age, body mass index (BMI), gestational age at examination, gestational age at delivery, fetal weight, cervical length, shear wave velocity (SWV), front lip SWV, back lip SWV, Young's modulus and SWE index. Heterogeneity of the assessment results was tested using Cochran's chi-square. RESULTS: A total of 13 articles were included. Age, BMI before delivery, gestational age (when gray-scale ultrasound was combined with SWE examination), gestational age at delivery, neonatal weight, cervical depth, SWV of placental margin, SWV of anterior lip, SWV of posterior lip and Young's modulus of the study group were significantly different from those of the control group. The elastic modulus of the perineal body and the SWE of the anterior lip of the study group were significantly higher than those of the control group [mean difference (MD) =8.11, 4.39, 95% confidence interval (CI): 3.90-12.31, 0.94-7.83; Z=3.78, 2.49, P=0.0002, 0.01]. The SWE of the posterior lip in the study group was significantly lower than that in the control group (MD =-4.34, 95% CI: -7.23 to 1.44; Z=2.93, P=0.003). DISCUSSION: The number of cases in the control group in the included articles was significantly more than that in the observation group, and there were fewer descriptions of gray-scale ultrasound combined with SWE indicators in the included articles. There may be a certain degree of bias for indicators without obvious heterogeneity, and further analysis was required through a large number of clinical verifications. However, this study can provide certain reference values for the diagnosis of primipara pregnancy.

The coupling of reduced type H vessels with unloading-induced bone loss and the protection role of Panax quinquefolium saponin in the male mice.

Unloading-induced bone loss is a critical complication characterized by the imbalance of bone formation and resorption induced by long-term confinement in bed or spaceflight. CD31hiEmcnhi (type H) vessel is a specific subtype of capillary, which was coupled with osteogenesis. However, the change of type H vessel and its contributions to the unloading-induced bone loss remains undisclosed. Herein, we found that bone formation and the number of type H vessels were synchronously reduced in the hindlimb-unloading (HU) mice. Panax quinquefolium saponin (PQS) could increase bone mass, osteoblast function and the number of type H vessels in the HU mice. In vitro, PQS treatment accelerated HMECs migration, augmented the total tube loops and increased the secretion of VEGF and Noggin. Primary osteoblasts function was obviously increased when treated with supernatant from PQS-treated HMECs. These effects of PQS were substantially counteracted when VEGF and Noggin in HMECs were knocked down by siRNA. These results demonstrated that unloading-induced bone loss is coupled with reduction of type H vessels and PQS performs preventive function via promoting type H vessel angiogenesis, which is closely associated with endothelial cell-derived VEGF and Noggin.

Ginsenoside Re Treatment Attenuates Myocardial Hypoxia/Reoxygenation Injury by Inhibiting HIF-1α Ubiquitination.

Previous studies have shown an attenuating effect of ginsenoside Re on myocardial injury induced by hypoxia/reoxygenation (H/R). However, the underlying mechanism remains unclear. This study was designed to determine the underlying mechanism by which ginsenoside Re protects from myocardial injury induced by H/R. HL-1 cells derived from AT-1 mouse atrial cardiomyocyte tumor line were divided into control, H/R, and H/R + ginsenoside Re groups. Cell viability was measured by CCK-8 assay. ATP levels were quantified by enzymatic assays. Signaling pathway was predicted by network pharmacology analyses and verified by luciferase assay and gene-silencing experiment. The relationship between ginsenoside Re and its target genes and proteins was analyzed by docking experiments, allosteric site analysis, real-time PCR, and ubiquitination and immunoprecipitation assays. Our results showed that ginsenoside Re treatment consistently increased HL-1 cell viability and significantly up-regulated ATP levels after H/R-induced injury. Network pharmacology analysis suggested that the effect of ginsenoside Re was associated with the regulation of the Hypoxia-inducing factor 1 (HIF-1) signaling pathway. Silencing of HIF-1α abrogated the effect of ginsenoside Re on HL-1 cell viability, which was restored by transfection with an HIF-1α-expressing plasmid. Results of the bioinformatics analysis suggested that ginsenoside Re docked at the binding interface between HIF-1α and the von Hippel-Lindau (VHL) E3 ubiquitin ligase, preventing VHL from binding HIF-1α, thereby inhibiting the ubiquitination of HIF-1α. To validate the results of the bioinformatics analysis, real-time PCR, ubiquitination and immunoprecipitation assays were performed. Compared with the mRNA expression levels of the H/R group, ginsenoside Re did not change expression of HIF-1α mRNA, while protein level of HIF-1α increased and that of HIF-1α[Ub]n decreased following ginsenoside Re treatment. Immunoprecipitation results showed that the amount of HIF-1α bound to VHL substantially decreased following ginsenoside Re treatment. In addition, ginsenoside Re treatment increased the expression of GLUT1 (glucose transporter 1) and REDD1 (regulated in development and DNA damage response 1), which are targets of HIF-1α and are critical for cell metabolism and viability. These results suggested that Ginsenoside Re treatment attenuated the myocardial injury induced by H/R, and the possible mechanism was associated with the inhibition of HIF-1α ubiquitination.

Recent Progress of Nanozymes in the Detection of Pathogenic Microorganisms.

Infectious diseases are among the world's principal health problems. It is crucial to develop rapid, accurate and cost-effective methods for the detection of pathogenic microorganisms. Recently, considerable progress has been achieved in the field of inorganic enzyme mimics (nanozymes). Compared with natural enzymes, nanozymes have higher stability and lower cost. More interestingly, their properties can be designed for various demands. Herein, we introduce the latest research progress on the detection of pathogenic microorganisms by using various nanozymes. We also discuss the current challenges of nanozymes in biosensing and provide some strategies to overcome these barriers.

Colorimetric determination of ascorbic acid using a polyallylamine-stabilized IrO2/graphene oxide nanozyme as a peroxidase mimic.

The authors describe a peroxidase-mimicking nanozyme composed of IrO2 and graphene oxide (GO). It was synthesized from monodisperse IrO2 nanoparticles with an average diameter of 1.7 ± 0.3 nm that were prepared by pulsed laser ablation in ethanol. The nanoparticles were then placed on polyallylamine-modified GO nanosheets through electrostatic interaction. The peroxidase-like activity of the resulting nanocomposites was evaluated by catalytic oxidation of 3,3',5,5'-tetramethylbenzidine in the presence of H2O2. Kinetic results demonstrated that the catalytic behavior of the nanocomposites follows Michaelis-Menten kinetics. Experiments performed with terephthalic acid and cytochrome C confirmed that the peroxidase-like activity originated from the electron transfer mechanism rather than from generation of hydroxy radicals. The peroxidase-like activity is inhibited in the presence of ascorbic acid (AA). Based on this property, a colorimetric assay was developed for the determination of AA by exploiting the peroxidase-like activity of IrO2/GO nanocomposites. The linear relationship between absorbance at 652 nm and the concentration of AA was acquired. The limit of detection for AA is 324 nM. Further applications of the method for AA detection in real samples were also successfully demonstrated. Graphical abstractSchematic of the preparation of polyallylamine (PAH)-stabilized IrO2/GO nanocomposites and the colorimetric detection of AA based on the peroxidase-like activity of IrO2/GO nanocomposites.

Short-Chain Fatty Acids Promote Intracellular Bactericidal Activity in Head Kidney Macrophages From Turbot (Scophthalmus maximus L.) via Hypoxia Inducible Factor-1α.

Short-chain fatty acids (SCFAs) are mainly produced by microbiota through the fermentation of carbohydrates in the intestine. Acetate, propionate, and butyrate are the most abundant SCFA metabolites and have been shown to be important in the maintenance of host health. In this study, head kidney macrophages (HKMs) were isolated and cultured from turbots. We found that the antibacterial activity of HKMs was increased after these cells were incubated with sodium butyrate, sodium propionate or sodium acetate. Interestingly, our results showed that all three SCFAs enhanced the expression of hypoxia inducible factor-1 α (HIF-1α) in HKMs, and further study confirmed that butyrate augmented the oxygen consumption of these cells. Moreover, HIF-1α inhibition diminished the butyrate-promoted intracellular bacterial killing activity of macrophages, and SCFAs also raised the gene expression and activity of lysozymes in HKMs via HIF-1α signaling. In addition, our results suggested that butyrate induced HIF-1α expression and the bactericidal activity of HKMs through histone deacetylase inhibition, while G protein-coupled receptors did not contribute to this effect. Finally, we demonstrated that butyrate induced a similar response in the murine macrophage cell line RAW264.7. In conclusion, our results demonstrated that SCFAs promoted HIF-1α expression via histone deacetylase inhibition, leading to the enhanced production of antibacterial effectors and increased bacterial killing of macrophages.

Using the UPLC-ESI-Q-TOF-MSE method and intestinal bacteria for metabolite identification in the nonpolysaccharide fraction from Bletilla striata.

Bletilla striata (Thunb.) Reichb. f. (Orchidaceae), also known as Bai-ji, is a traditional Chinese herb that is widely used in Asia to treat hematemesis, hemoptysis, traumatic bleeding and other similar disorders. Most studies have focused on the pharmacological activities of polysaccharide extracts from B. striata. Our previous studies found that the nonpolysaccharide fraction from B. striata extract also has a hemostatic effect; however, the active constituents responsible for this pharmacological action are unclear. Thus, the metabolic profiles of the nonpolysaccharide fraction were investigated in Sprague-Dawley rats and intestinal bacteria models using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Mass data were acquired by the MSE method. Eight components including five prototypes and three metabolites were identified in rat biofluids after oral administration of the nonpolysaccharide fraction. The parent compounds underwent various metabolic processes, including hydrolysis, deglucosylation, glycosylation and sulfate conjugation. The results not only reveal the possible metabolic pathway, but also indicate the potential pharmacological components. Further mechanistic studies using nonpolysaccharide compounds of the B. striata extract are required to obtain potential candidate compounds.

Integration of Both Invariable and Tunable Microwave Magnetisms in a Single Flexible La0.67Sr0.33MnO3 Thin Film.

High-quality flexible magnetic oxide thin films have promoted a wide range of potential applications in spintronic devices due to their unique physical properties. To obtain the optimized microwave magnetism for future all-oxide-based spintronic applications, high-quality oxide materials with excellent epitaxial quality as well as specific bending properties related to ferromagnetic resonance are high in demand. Here, (001)-oriented La0.67Sr0.33MnO3 epitaxial thin films with different thicknesses have been grown and subsequently transferred onto flexible poly(dimethylsiloxane) substrates. The microwave magnetisms of these film samples have been investigated under various bending states. Under bending, the ferromagnetic resonance lineshape of the film gradually transits from a single mode to a superposition of multimodes, possibly because of the uneven distribution of magnetization in the bending film at X-band. This phenomenon is more apparent when the direction of the applied magnetic field goes close to the out-of-plane of the film. Hence, an integration of invariable and continuous tuning of ferromagnetic resonance field under various mechanical bending can be achieved in one same sample by just tuning the direction of the applied magnetic field, which reveals that the flexible La0.67Sr0.33MnO3 thin films have huge potential in the applications in future flexible multifunctional devices.

A Validated HPLC-MS/MS Method for Simultaneous Determination of Militarine and Its Three Metabolites in Rat Plasma: Application to a Pharmacokinetic Study.

A rapid, reliable, and sensitive HPLC-electrospray ionization-tandem mass spectrometry (HPLC-MS/MS) method was established and validated for simultaneous determination of militarine and its three metabolites (gastrodin, α-isobutylmalic acid, and gymnoside I) in rat plasma. Plasma was acidified with formic acid, and protein was precipitated with methanol. MS/MS with ESI and multiple reaction monitoring at m/z 725.3→457.3, 457.1→127, 304.3→107.2, 189→129, and 417.1→267.1 was used for determination of militarine, gastrodin, α-isobutylmalic acid, gymnoside I, and puerarin (internal standard), respectively. Chromatographic separation was conducted using an ACE UltraCore SuperC18 (2.1 × 100 mm, 2.5 µm) column with gradient mobile phase (0.1% formic acid in water and acetonitrile). The lower limits of quantitation for militarine, gastrodin, α-isobutylmalic acid, and gymnoside I were 1.02, 2.96, 1.64, and 0.3 ng/mL, respectively. The relative standard deviations of intra- and interday measurements were less than 15%, and the method accuracy ranged from 87.4% to 112.5%. The extraction recovery was 83.52%-105.34%, and no matrix effect was observed. The three metabolites (gastrodin, α-isobutylmalic acid, and gymnoside I) were synchronously detected at 0.83 h, suggesting that militarine was rapidly transformed to gastrodin, α-isobutylmalic acid, and gymnoside I. Moreover, the area under the curve (AUC) and Cmax of militarine were significantly lower than those of gastrodin and α-isobutylmalic acid, showing that militarine was largely metabolized to gastrodin and α-isobutylmalic acid in vivo. The studies on pharmacokinetics of militarine and its three metabolites were of great use for facilitating the clinical application of militarine and were also highly meaningful for the potential development of militarine.

Voltage-Driven Room-Temperature Resistance and Magnetization Switching in Ceramic TiO2/PAA Nanoporous Composite Films.

Voltage control of room-temperature ferromagnetism has remained a big challenge which will greatly influence the multifunctional memory devices. In this paper, porous TiO2 thin films were deposited by dc-reactive magnetron sputtering onto ordered porous anodic alumina (PAA) substrates. Voltage-driving room-temperature resistance and magnetization switching without external magnetic field are simultaneously found in an Ag/TiO2/PAA/Al (Ag/TP/Al) device. Further analysis indicates that the formation/rupture of oxygen vacancy defect-based conductive filaments would be responsible for the changes of resistivity and magnetization. Our present results suggest that the TP nanoporous composite film material may therefore be used to achieve voltage control of magnetism and resistance switching in the future multifunctional memory devices. The Ag/TP/Al devices can also be used for new spintronic devices, neuromorphic operations, and alternative logic circuits and computing.

Panax quinquefolium saponin attenuates cardiac remodeling induced by simulated microgravity.

BACKGROUND: Cardiac atrophy and reduced cardiac distensibility have been reported following space flight. Cardiac function is correspondingly regulated in response to changes in loading conditions. Panax quinquefolium saponin (PQS) improves ventricular remodeling after acute myocardial infarction by alleviating endoplasmic reticulum stress and Ca2+overload. However, whether PQS can ameliorate cardiac atrophy following exposure to simulated microgravity remains unknown. PURPOSE: To explore the protective role of PQS in cardiac remodeling under unloading conditions and its underlying mechanisms. METHODS: Hindlimb unloading (HU) model was used to simulate unloading induced cardiac remodeling. Forty-eight male rats were randomly assigned to four groups, including control, PQS, HU and HU + PQS. At 8 weeks after the experiment, cardiac structure and function, serum levels of Creatine Kinase-MB (CK-MB), Cardiactroponin T (cTnT), ischemia modified albumin (IMA), and cardiomyocyte apoptosis were measured. Network pharmacology analysis was used to predict the targets of the six major constituents of PQS, and the signaling pathways they involved in were analyzed by bioinformatics methods. Changes in the key proteins involved in the protective effects of PQS were further confirmed by Western Blot. RESULTS: Simulated microgravity led to increases in serum levels of CK-MB, cTnT and IMA, remodeling of cardiac structure, impairment of cardiac function, and increased cardiomyocyte apoptosis as compared with control. PQS treatment significantly reduced serum levels of CK-MB, cTnT and IMA, improved the impaired cardiac structure and function, and decreased cardiomyocyte apoptosis induced by unloading. The activation of AMPK and inhibition of Erk1/2 and CaMKII/HDAC4 were demonstrated in the cardiocytes of HU rats after PQS treatment. CONCLUSION: PQS provides protection against cardiac remodeling induced by simulated microgravity, partly resulting from changes in the signaling pathways related to energy metabolism reduction, calcium overloading and cell apoptosis.

Myocardial CKIP-1 Overexpression Protects from Simulated Microgravity-Induced Cardiac Remodeling.

Human cardiovascular system has adapted to Earth's gravity of 1G. The microgravity during space flight can induce cardiac remodeling and decline of cardiac function. At present, the mechanism of cardiac remodeling induced by microgravity remains to be disclosed. Casein kinase-2 interacting protein-1 (CKIP-1) is an important inhibitor of pressure-overload induced cardiac remodeling by decreasing the phosphorylation level of HDAC4. However, the role of CKIP-1 in the cardiac remodeling induced by microgravity is unknown. The purpose of this study was to determine whether CKIP-1 was also involved in the regulation of cardiac remodeling induced by microgravity. We first detected the expression of CKIP-1 in the heart from mice and monkey after simulated microgravity using Q-PCR and western blotting. Then, myocardial specific CKIP-1 transgenic (TG) and wild type mice were hindlimb-suspended (HU) to simulate microgravity effect. We estimated the cardiac remodeling in morphology and function by histological analysis and echocardiography. Finally, we detected the phosphorylation of AMPK, ERK1/2, and HDAC4 in the heart from wild type and CKIP-1 transgenic mice after HU. The results revealed the reduced expression of CKIP-1 in the heart both from mice and monkey after simulated microgravity. Myocardial CKIP-1 overexpression protected from simulated microgravity-induced decline of cardiac function and loss of left ventricular mass. Histological analysis demonstrated CKIP-1 TG inhibited the decreases in the size of individual cardiomyocytes of mice after hindlimb unloading. CKIP-1 TG can inhibit the activation of HDAC4 and ERK1/2 and the inactivation of AMPK in heart of mice induced by simulated microgravity. These results demonstrated CKIP-1 was a suppressor of cardiac remodeling induced by simulated microgravity.