20(S)-protopanaxatriol inhibited D-galactose-induced brain aging in mice via promoting mitochondrial autophagy flow.

Previous reports have confirmed that saponins (ginsenosides) derived from Panax ginseng. C. A. Meyer exerted obvious memory-enhancing and antiaging effects, and the simpler the structure of ginsenosides, the better the biological activity. In this work, we aimed to explore the therapeutic effect and underlying molecular mechanism of 20(S)-protopanaxatriol (PPT), the aglycone of panaxatriol-type ginsenosides, by establishing D-galactose (D-gal)-induced subacute brain aging model in mice. The results showed that PPT treatment (10 and 20 mg/kg) for 4 weeks could significantly restore the D-gal (800 mg/kg for 8 weeks)-induced impaired memory function, choline dysfunction, and redox system imbalance in mice. Meanwhile, PPT also significantly reduced the histopathological changes caused by D-gal exposure. Moreover, PPT could increase TFEB/LAMP2 protein expression to promote mitochondrial autophagic flow. Importantly, the results from molecular docking showed that PPT had good binding ability with LAMP2 and TFEB, suggesting that TFEB/LAMP2 might play an important role in PPT to alleviate D-gal-caused brain aging.

Lappaol F regulates the cell cycle by activating CDKN1C/p57 in human colorectal cancer cells.

CONTEXT: Lappaol F (LAF), a natural lignan from Arctium lappa Linné (Asteraceae), inhibits tumor cell growth in vitro and in vivo. The underlying mechanism involves the suppression of the Yes-associated protein. However, the specific role of LAF in cell cycle regulation remains unknown. OBJECTIVE: This study determined the molecular mechanism by which LAF regulates cell cycle progression. MATERIALS AND METHODS: Various colon cancer cell lines (SW480, HCT15, and HCT116) were treated with LAF (25, 50, and 75 µmol/L) for 48 h. The effects of LAF on cell proliferation and cell cycle were determined using sulforhodamine B and flow cytometry assays. Differentially expressed proteins (DEPs) were identified using quantitative proteomics. Bioinformatic analysis of DEPs was conducted via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Expression levels of DEPs in the cell cycle pathway were analyzed using RT-qPCR and western blotting. RESULTS: LAF suppressed the proliferation of SW480, HCT15, and HCT116 cells (IC50 47.1, 51.4, and 32.8 µmol/L, respectively) and induced cell cycle arrest at the S phase. A total of 6331 proteins were identified and quantified, of which 127 were differentially expressed between the LAF-treated and untreated groups. GO and KEGG enrichment analyses revealed that DEPs mainly participated in the cell cycle. CDKN1C/p57 showed the most significant differential expression, with the highest fold-change (3.155-fold). Knockdown of CDKN1C/p57 attenuated the S phase cell cycle arrest and proliferation inhibition induced by LAF. CONCLUSION: LAF exerts antitumor effects via S phase arrest by activating CDKN1C/p57 in colorectal cancer cells.

Transcriptomic analysis reveals the regulatory mechanism underlying the indirubin-mediated amelioration of dextran sulfate sodium-induced colitis in mice.

CONTEXT: Aryl hydrocarbon receptor (AhR) agonists are potential therapeutic agents for ulcerative colitis (UC). Indirubin (IDR), which is a natural AhR ligand approved for leukemia treatment, ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the therapeutic mechanisms of IDR are unknown, limiting its application. OBJECTIVE: This study explores the therapeutic mechanisms of IDR in DSS-induced colitis using transcriptomic analysis. MATERIALS AND METHODS: Male BALB/c mice were categorized to six groups: normal, DSS model (2% DSS), IDR treatment (10, 20 and 40 mg/kg), and sulfasalazine (520 mg/kg) groups. The drugs were intragastrically administered for 7 consecutive days. The disease activity index (DAI) was recorded. After euthanasia, the colon length was measured, and histopathological examination, immunohistochemistry staining using F4/80, and colonic transcriptomic analysis were conducted. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting (WB) were conducted to verify our findings. RESULTS: Compared with DSS, IDR treatment decreased the DAI score by 64.9% and increased colon length by 26.2%. Moreover, it alleviated mucosal injury and reduced macrophage infiltration. Transcriptomic analysis identified several downregulated genes (Igkvs and Nlrp3), as well as Nlrp3/Il1ß and hemoglobin gene networks, after IDR treatment. The abundances of NF-κB p65, NLRP3, IL-1ß, and HBA decreased by 69.1, 59.4, 81.1, and 83.0% respectively, after IDR treatment. DISCUSSION AND CONCLUSION: Apart from the well-documented NF-κB signalling pathway, IL-17A, and NLRP3-IL-1ß, the suppression of haemoglobin-induced lipid peroxidation could be a previously unknown mechanism of IDR. Our study can help improve its application for UC treatment.

Long-term exercise at different intensities can reduce the inflammatory response in the brains of methamphetamine-treated mice.

Methamphetamine (METH) is a highly addictive psychoactive drug that is used worldwide. Various approaches have been used to address METH dependence, but many of them have little effect. Previous studies have shown that exercise on a treadmill could reduce METH dependence in mice, but the intensity and duration of exercise that was needed to be effective was unknown. This study investigated the effects of low- and medium-intensity treadmill exercise on methamphetamine reward in male mice via conditioned place preference (CPP) training, and the levels of the inflammatory factors IL-1ß, IL-6 and TNF-α in three brain regions (cerebral cortex, hippocampus and striatum) were determined. The results showed that long-term medium-intensity exercise reduced the effects of methamphetamine on inflammation markers in the brain and CPP scores. In addition, long-term medium-intensity exercise decreased IL-1ß concentrations in the cerebral cortex and hippocampus, reduced IL-6 concentrations in the striatum, and reduced TNF-α concentrations in the cerebral cortex, hippocampus, and striatum in methamphetamine-treated mice; low-intensity exercise was less effective. The results indicated that long-term medium-intensity exercise could reduce concentrations of methamphetamine-induced encephalitis factors in male mice, while low-intensity exercise was less effective in alleviating dependence and inflammatory responses. It is suggested that exercise intensity is an important factor affecting the dependence level and inflammatory responses in the brain in mice administered methamphetamine.

Brain white matter extracellular free-water increases are related to reduced neurocognitive function in systemic lupus erythematosus.

OBJECTIVES: Brain white matter (WM) microstructural changes evaluated by diffusion MRI are well documented in patients with SLE. Yet, the conventional diffusion tensor imaging technique fails to differentiate WM changes that originate from tissue alterations from those due to increased extracellular free water (FW) related to neuroinflammation, microvascular disruption, atrophy, or other extracellular processes. Here, we sought to delineate changes in WM tissue microstructure and extracellular FW volume and examine their relationships with neurocognitive function in SLE patients. METHODS: Twenty SLE patients [16 females, aged 36.0 (10.6)] without clinically overt neuropsychiatric manifestation and 61 healthy controls (HCs) [29 females, aged 29.2 (9.4)] underwent diffusion MRI and computerized neuropsychological assessments cross-sectionally. The FW imaging method was applied to compare microstructural tissue changes and extracellular FW volume of the brain WM between SLE patients and HCs. Association between extracellular FW changes and neurocognitive performance was studied. RESULTS: SLE patients had higher WM extracellular FW compared with HCs (family-wise-error-corrected P < 0.05), while no group difference was found in FW-corrected tissue compartment and structural connectivity metrics. Extracellular FW increases in SLE patients were associated with poorer neurocognitive performance that probed sustained attention (P = 0.022) and higher cumulative glucocorticoid dose (P = 0.0041). Such findings remained robust after controlling for age, gender, intelligence quotient, and total WM volume. CONCLUSION: The association between WM extracellular FW increases and reduced neurocognitive performance suggest possible microvascular degradation and/or neuroinflammation in SLE patients with clinically inactive disease. The mechanistic impact of cumulative glucocorticoids on WM FW deserves further evaluation.

Boosting scRNA-seq data clustering by cluster-aware feature weighting.

BACKGROUND: The rapid development of single-cell RNA sequencing (scRNA-seq) enables the exploration of cell heterogeneity, which is usually done by scRNA-seq data clustering. The essence of scRNA-seq data clustering is to group cells by measuring the similarities among genes/transcripts of cells. And the selection of features for cell similarity evaluation is of great importance, which will significantly impact clustering effectiveness and efficiency. RESULTS: In this paper, we propose a novel method called CaFew to select genes based on cluster-aware feature weighting. By optimizing the clustering objective function, CaFew obtains a feature weight matrix, which is further used for feature selection. The genes have large weights in at least one cluster or the genes whose weights vary greatly in different clusters are selected. Experiments on 8 real scRNA-seq datasets show that CaFew can obviously improve the clustering performance of existing scRNA-seq data clustering methods. Particularly, the combination of CaFew with SC3 achieves the state-of-art performance. Furthermore, CaFew also benefits the visualization of scRNA-seq data. CONCLUSION: CaFew is an effective scRNA-seq data clustering method due to its gene selection mechanism based on cluster-aware feature weighting, and it is a useful tool for scRNA-seq data analysis.

Value of quantitative analysis of left ventricular systolic function in patients on maintenance hemodialysis based on myocardial work technique.

BACKGROUND: This study aimed to determine the left ventricular (LV) systolic function in patients on maintenance hemodialysis (MHD) using the myocardial work (MW) technique and investigate the clinical value of the MW technique for the quantitative analysis of left ventricular (LV) systolic function in MHD patients with left ventricular hypertrophy (LVH). METHODS: A total of 68 MHD patients and 35 controls were registered in this study. The MHD patients were divided into the non-left ventricular hypertrophy (NLVH) group (n = 35) and the LVH group (n = 33) according to the LV mass index (LVMI). MW was used to generate the LV global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), and global wasted work (GWW), global work efficiency (GWE). GLS and the MW parameters (GWI, GCW, GWW, GWE) were compared between groups and the correlations between these parameters and the LV ejection fraction (LVEF) in the LVH group were examined. The receiver operating characteristic (ROC) curve was used to evaluate the efficacy of MW parameters and GLS for the assessment of LV systolic dysfunction in MHD with LVH patients. RESULTS: The LVH group had significantly lower GWE, GWI, GCW, and GLS but higher GWW than the control and NLVH groups. Compared with the control group, the NLVH group had significantly lower GWE and GLS and higher GWW, but no significant differences in GWI, GCW were observed between these two groups. The LVEF was negatively correlated with GWW in MHD patients, but positively correlated with GWI, GWE, and GCW in the LVH group. Receiver operating characteristic curve (ROC) analysis revealed that GWE, GWW, GWI, and GCW had appreciable area under the curve (AUC), sensitivity, and specificity for evaluating LV function in LVH patients on MHD. CONCLUSIONS: The MW parameters can quantitatively represent the LV myocardial work in MHD patients. Thus, the technique provides a new method for the quantitative evaluation of LV systolic function in MHD with LVH patients.

DDoS Flood and Destination Service Changing Sensor.

In this paper, we aim to detect distributed denial of service (DDoS) attacks, and receive a notification of destination service, changing immediately, without the additional efforts of other modules. We designed a kernel-based mechanism to build a new Transmission Control Protocol/Internet Protocol (TCP/IP) connection smartly by the host while the users or clients not knowing the location of the next host. Moreover, we built a lightweight flooding attack detection mechanism in the user mode of an operating system. Given that reinstalling a modified operating system on each client is not realistic, we managed to replace the entry of the system call table with a customized sys_connect. An effective defense depends on fine detection and defensive procedures. In according with our experiments, this novel mechanism can detect flooding DDoS successfully, including SYN flood and ICMP flood. Furthermore, through cooperating with a specific low cost network architecture, the mechanism can help to defend DDoS attacks effectively.

Echocardiographic evaluation of the elasticity of the ascending aorta in patients with essential hypertension.

BACKGROUND: Hypertension is the most common chronic disease and the most important risk factor for cardiovascular and cerebrovascular diseases. Atheroma and arteriosclerosis plays a key role in the occurrence and development of hypertension. The purpose of this study was to evaluate the elasticity of ascending aorta wall in patients with essential hypertension (EH) using M-mode echocardiography. MATERIALS AND METHODS: We prospectively enrolled 54 EH patients and 51 healthy subjects (HS). They all underwent transthoracic echocardiography to measure ascending aorta inner diameters and brachial blood pressure measurement to calculate aortic elastic variables: compliance, distensibility, strain, stiffness index, and Peterson's elastic modulus. All participants also underwent bilateral carotid ultrasonographic examination. RESULTS: There were no significant differences in age, sex, body mass index, blood lipids, blood glucose, and ascending aorta inner diameters between the two groups. We found neither intimal thickening nor plaque formation in the left or right carotid arteries in both groups. The aortic elastic properties were significantly impaired in EH patients compared with HS. CONCLUSIONS: Echocardiography can be used for the noninvasive evaluation of ascending aorta wall elasticity as an early screening technique. Subclinical arteriosclerosis appeared to occur in the ascending aorta of patients with essential hypertension even though carotid ultrasonography was normal.

Effects and Mechanisms of Chitosan and ChitosanOligosaccharide on Hepatic Lipogenesis and Lipid Peroxidation, Adipose Lipolysis, and Intestinal Lipid Absorption in Rats with High-Fat Diet-Induced Obesity.

Chitosan and its derivative, chitosan oligosaccharide (CO), possess hypolipidemic and anti-obesity effects. However, it is still unclear if the mechanisms are different or similar between chitosan and CO. This study was designed to investigate and compare the effects of CO and high-molecular-weight chitosan (HC) on liver lipogenesis and lipid peroxidation, adipose lipolysis, and intestinal lipid absorption in high-fat (HF) diet-fed rats for 12 weeks. Rats were divided into four groups: normal control diet (NC), HF diet, HF diet+5% HC, and HF diet+5% CO. Both HC and CO supplementation could reduce liver lipid biosynthesis, but HC had a better effect than CO on improving liver lipid accumulation in HF diet-fed rats. The increased levels of triglyceride decreased lipolysis rate, and increased lipoprotein lipase activity in the perirenal adipose tissue of HF diet-fed rats could be significantly reversed by both HC and CO supplementation. HC, but not CO, supplementation promoted liver antioxidant enzymes glutathione peroxidase and superoxide dismutase activities and reduced liver lipid peroxidation. In the intestines, CO, but not HC, supplementation reduced lipid absorption by reducing the expression of fabp2 and fatp4 mRNA. These results suggest that HC and CO have different mechanisms for improving lipid metabolism in HF diet-fed rats.

Lappaol F, an anticancer agent, inhibits YAP via transcriptional and post-translational regulation.

CONTEXT: Lappaol F (LAF), a natural lignan from Arctium lappa Linné (Asteraceae), inhibits tumour cell growth by inducing cell cycle arrest. However, its underlying anticancer mechanism remains unclear. OBJECTIVE: The effects of LAF on the Hippo-Yes-associated protein (YAP) signalling pathway, which plays an important role in cancer progression, were explored in this study. MATERIALS AND METHODS: Cervical (HeLa), colorectal (SW480), breast (MDA-MB-231) and prostate (PC3) cancer cell lines were treated with LAF at different concentrations and different durations. BALB/c nude mice bearing colon xenografts were intravenously injected with vehicle, LAF (10 or 20 mg/kg) or paclitaxel (10 mg/kg) for 15 days. The expression and nuclear localisation of YAP were analysed using transcriptome sequencing, quantitative PCR, western blotting and immunofluorescence. RESULTS: LAF suppressed the proliferation of HeLa, MDA-MB-231, SW480 and PC3 cells (IC50 values of 41.5, 26.0, 45.3 and 42.9 µmol/L, respectively, at 72 h), and this was accompanied by significant downregulation in the expression of YAP and its downstream target genes at both the mRNA and protein levels. The expression of 14-3-3σ, a protein that causes YAP cytoplasmic retention and degradation, was remarkably increased, resulting in a decrease in YAP nuclear localisation. Knockdown of 14-3-3σ with small interfering RNA partially blocked LAF-induced YAP inhibition and anti-proliferation effects. In colon xenografts, treatment with LAF led to reduced YAP expression, increased tumour cell apoptosis and tumour growth inhibition. CONCLUSION: LAF was shown to be an inhibitor of YAP. It exerts anticancer activity by inhibiting YAP at the transcriptional and post-translational levels.

In Vitro Inhibition of Human Aldehyde Oxidase Activity by Clinically Relevant Concentrations of Gefitinib and Erlotinib: Comparison with Select Metabolites, Molecular Docking Analysis, and Impact on Hepatic Metabolism of Zaleplon and Methotrexate.

Gefitinib and erlotinib are epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) with activity against metastatic non-small cell lung cancer. Aldehyde oxidase-1 (AOX1) is a cytosolic drug-metabolizing enzyme. We conducted an experimental and molecular docking study on the effect of gefitinib, erlotinib, and select metabolites on the in vitro catalytic activity of AOX1, as assessed by carbazeran 4-oxidation, and determined the impact of AOX1 inhibition on hepatic metabolism of zaleplon and methotrexate. Gefitinib, desmorpholinopropylgefitinib, erlotinib, desmethylerlotinib, and didesmethylerlotinib inhibited human hepatic cytosolic carbazeran 4-oxidation by a competitive mode, with inhibition constants in submicromolar or low micromolar concentrations. Desmethylgefitinib did not affect AOX1 catalytic activity. A similar pattern was obtained when investigated with human kidney cytosol or recombinant AOX1. The differential effect of gefitinib on human, rat, and mouse hepatic AOX1 catalytic activity suggests species-dependent chemical inhibition of AOX1. Erlotinib was considerably more potent than gefitinib in decreasing hepatic cytosolic zaleplon 5-oxidation and methotrexate 7-oxidation. Molecular docking analyses provided structural insights into the interaction between EGFR-TKIs and AOX1, with key residues and bonds identified, which provided favorable comparison and ranking of potential inhibitors. Based on the US Food and Drug Administration guidance to assess the risk of drug-drug interactions, the calculated R1 values indicate that further investigations are warranted to determine whether gefitinib and erlotinib impact AOX1-mediated drug metabolism in vivo. Overall, erlotinib desmethylerlotinib, didesmethylerlotinib, gefitinib, and desmorpholinopropylgefitinib are potent inhibitors of human AOX1 catalytic function and hepatic metabolism of zaleplon and methotrexate, potentially affecting drug efficacy or toxicity. SIGNIFICANCE STATEMENT: As epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib are first-line pharmacotherapy for metastatic non-small cell lung cancer. Our experimental findings indicate that clinically relevant concentrations of gefitinib, desmorpholinopropylgefitinib, erlotinib, desmethylerlotinib, and didesmethylerlotinib, but not desmethylgefitinib, inhibit human aldehyde oxidase (AOX1) catalytic activity and hepatic cytosolic metabolism of zaleplon and methotrexate. Molecular docking analysis provide structural insights into the key AOX1 interactions with these EGFR-TKIs. Our findings may trigger improved strategies for new EGFR-TKI design and development.

Effects of Chitosan Oligosaccharide on Plasma and Hepatic Lipid Metabolism and Liver Histomorphology in Normal Sprague-Dawley Rats.

Chitosan oligosaccharide is known to ameliorate hypercholesterolemia and diabetes. However, some studies found that chitosan oligosaccharide might induce mild to moderate hepatic damage in high-fat (HF) diet-induced obese rats or diabetic rats. Chitosan oligosaccharide can be as a dietary supplement, functional food, or drug. Its possible toxic effects to normal subjects need to be clarified. This study is designed to investigate the effects of chitosan oligosaccharide on plasma and hepatic lipid metabolism and liver histomorphology in normal Sprague-Dawley rats. Diets supplemented with 5% chitosan oligosaccharide have been found to induce liver damage in HF diet-fed rats. We therefore selected 5% chitosan oligosaccharide as an experimental object. Rats were divided into: a normal control diet group and a normal control diet +5% chitosan oligosaccharide group. The experimental period was 12 weeks. The results showed that supplementation of 5% chitosan oligosaccharide did not significantly change the body weight, food intake, liver/adipose tissue weights, plasma lipids, hepatic lipids, plasma levels of AST, ALT, and TNF-α/IL-6, hepatic lipid peroxidation and anti-oxidative enzyme activities, fecal lipids, and liver histomorphology in normal rats. These findings suggest that supplementation of 5% chitosan oligosaccharide for 12 weeks may not induce lipid metabolism disorder and liver toxicity in normal rats.

Wearable Activity Trackers for Monitoring Adherence to Home Confinement During the COVID-19 Pandemic Worldwide: Data Aggregation and Analysis.

BACKGROUND: In the context of home confinement during the coronavirus disease (COVID-19) pandemic, objective, real-time data are needed to assess populations' adherence to home confinement to adapt policies and control measures accordingly. OBJECTIVE: The aim of this study was to determine whether wearable activity trackers could provide information regarding users' adherence to home confinement policies because of their capacity for seamless and continuous monitoring of individuals' natural activity patterns regardless of their location. METHODS: We analyzed big data from individuals using activity trackers (Withings) that count the wearer's average daily number of steps in a number of representative nations that adopted different modalities of restriction of citizens' activities. RESULTS: Data on the number of steps per day from over 740,000 individuals around the world were analyzed. We demonstrate the physical activity patterns in several representative countries with total, partial, or no home confinement. The decrease in steps per day in regions with strict total home confinement ranged from 25% to 54%. Partial lockdown (characterized by social distancing measures such as school closures, bar and restaurant closures, and cancellation of public meetings but without strict home confinement) does not appear to have a significant impact on people's activity compared to the pre-pandemic period. The absolute level of physical activity under total home confinement in European countries is around twofold that in China. In some countries, such as France and Spain, physical activity started to gradually decrease even before official commitment to lockdown as a result of initial less stringent restriction orders or self-quarantine. However, physical activity began to increase again in the last 2 weeks, suggesting a decrease in compliance with confinement orders. CONCLUSIONS: Aggregate analysis of activity tracker data with the potential for daily updates can provide information regarding adherence to home confinement policies.

Peak systolic longitudinal rotation: a new tool for detecting left ventricular systolic function in patients with type 2 diabetes mellitus by two-dimensional speckle tracking echocardiography.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is one of the most prevalent cardiac and cerebrovascular risk factors. The study aimed to find a new way to investigate left ventricle (LV) systolic dysfunction in T2DM patients using two-dimensional speckle tracking echocardiography (2D-STE). METHODS: Fifty-one untreated T2DM patients and 52 normal control subjects were enrolled for the research. Apical four-chamber view was acquired by two-dimensional echocardiography. Segmental and global peak systolic longitudinal rotation (PSLR) degrees were measured by the software of EchoPAC. RESULTS: In T2DM patients, global PSLR prominently rotated clockwise, while in normal subjects, global PSLR degrees were so small and almost had no PSLR. HBA1c negatively correlated with apex and global PSLR, that is, T2DM patients with higher HBA1c had a larger clockwise apex and global PSLR. ROC analysis showed that PSLR could detect the accuracy of LV systolic dysfunction. CONCLUSION: Cardiac clockwise global PSLR was found in T2DM patients. The cardiac contractile function in T2DM patients was impaired. The new tool of PSLR can conveniently detect cardiac systolic dysfunction in T2DM patients. HBA1c could predict systolic dysfunction in T2DM patients.

PhosD: inferring kinase-substrate interactions based on protein domains.

MOTIVATION: Identifying the kinase-substrate relationships is vital to understanding the phosphorylation events and various biological processes, especially signal transductions. Although large amount of phosphorylation sites have been detected, unfortunately, it is rarely known which kinases activate those sites. Despite distinct computational approaches have been proposed to predict the kinase-substrate interactions, the prediction accuracy still needs to be improved. RESULTS: In this paper, we propose a novel probabilistic model named as PhosD to predict kinase-substrate relationships based on protein domains with the assumption that kinase-substrate interactions are accomplished with kinase-domain interactions. By further taking into account protein-protein interactions, our PhosD outperforms other popular approaches on several benchmark datasets with higher precision. In addition, some of our predicted kinase-substrate relationships are validated by signaling pathways, indicating the predictive power of our approach. Furthermore, we notice that given a kinase, the more substrates are known for the kinase the more accurate its predicted substrates will be, and the domains involved in kinase-substrate interactions are found to be more conserved across proteins phosphorylated by multiple kinases. These findings can help develop more efficient computational approaches in the future. AVAILABILITY AND IMPLEMENTATION: The data and results are available at http://comp-sysbio.org/phosd. CONTACT: xm_zhao@tongji.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Evidence that growth hormone can improve mitochondrial function in oocytes from aged mice.

Decline in successful conception decreases more rapidly after 38 years of age owing to follicular depletion and decreased oocyte quality. However, limited information is available regarding the underlying mechanism and the useful treatment. This study aimed to evaluate the effects of growth hormone supplementation on oocyte maturation in vivo in aged and young mice and to determine its effect on mitochondrial function. The influence of three different doses of recombinant human growth hormone (rhGH) (0.4, 0.8 and 1.6 mg/kg/day) for 8 weeks before ovarian stimulation was analyzed. Superovulated oocytes were released from the oviduct of 12-week-old and 40-week-old female C57BL/6J mice 14-16 h after administration of human chorionic gonadotropin. Ovarian follicle and morphological analysis and oocyte maturation parameters were then evaluated. This study is the first, to our knowledge, to report that medium- and high-dose rhGH significantly increases antral follicles in aged mice but anti-Müllerian hormone (AMH) levels. Furthermore, derived oocytes, MII-stage oocyte rate, ATP levels, mitochondrial membrane potential and frequencies of homogeneous mitochondrial distribution increased. In contrast, in both aged and young mice, the mtDNA copy numbers per oocyte were similar before rhGH administration, and upon saline administration, they did not differ significantly. We conclude that medium-dose rhGH supplementation before standard ovarian stimulation regimens improves oocyte quality in aged mice, probably by enhancing mitochondrial functionality.

Left ventricular short-axis systolic function changes in patients with hypertrophic cardiomyopathy detected by two-dimensional speckle tracking imaging.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic disease was characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, fiber disarray. The short-axis systolic function is important in left ventricle function. METHODS: Forty one healthy subjects and 37 HCM patients were enrolled for this research. Parasternal short-axis at the basal, middle, and apical levels were acquired by Echocardiography. The peak systolic circumferential strain of the endocardial, the middle and the epicardial layers, the peak systolic radial strain, and the peak systolic rotational degrees at different short-axis levels were measured by 2-dimensional speckle tracking imaging (2D-STI). RESULTS: The peak systolic circumferential strain of the septum and anterior walls in HCM patients was significantly lower than normal subjects. All of the peak systolic radial strain in HCM patients was significantly lower than normal subjects. The rotational degrees at the base and middle short-axis levels in HCM patients were larger than normal subjects. The interventricular septal thickness in end-diastolic period correlated to the peak systolic circumferential strain of the septum wall. CONCLUSIONS: The short-axis systolic function was impaired in HCM patients. The peak circumferential systolic strain of the different layers, peak systolic radial strain and rotation degrees of the different short-axis levels detected by 2D-STI are very feasible for assessing the short-axis function in HCM patients.

Left ventricular systolic function changes in hypertrophic cardiomyopathy patients detected by the strain of different myocardium layers and longitudinal rotation.

BACKGROUND: Impairment of left ventricular (LV) longitudinal function has an important role in hypertrophic cardiomyopathy (HCM). This research investigated an association between the longitudinal strain of different myocardial layers, longitudinal rotation and the LV systolic function of HCM patients. METHODS: The research was performed on 36 HCM patients and 36 healthy subjects. The peak systolic longitudinal strain of the subendocardial, midmyocardial, and subepicardial layers was measured using 2-dimensional speckle tracking echocardiography (2D-STE). The apical long-axis and 4- and 2- chamber views were acquired via 2D Doppler echocardiography. The curve of the longitudinal rotation was traced at 17 timepoints in the analysis of 2 cardiac cycles. RESULTS: Compared with healthy subjects, in HCM patients regional LV peak systolic longitudinal strain was less, not only in hypertrophied LV myocardium, but also in non-hypertrophied myocardium. The rotational degrees of the midmyocardial-septal, apex, and lateral wall of HCM patients were significantly different from that of normal subjects, as follows. In HCM patients, clockwise longitudinal rotation was found. The interventricular septum thickness at end-diastole positively correlated with the peak longitudinal systolic strain of the subendocardial, the midmyocardial, and the subepicardial layers. The area under ROC curve values for subendocardial, midmyocardial and subepicardial layers in HCM patients were 0.923, 0.938, 0.948. CONCLUSION: In HCM patients, the longitudinal function was damaged, even with normal LV ejection fraction. The peak longitudinal systolic strain of the subendocardial, midmyocardial, and subepicardial layers, and the longitudinal rotation detected by 2D-STE, are very sensitive predictors of systolic function in patients with HCM.