Disturbed Energy Metabolism Research Articles

Influence of microplastics on triclosan bioaccumulation and metabolomics variation in Tilapia fish tissues.

Microplastics (MPs) and chemical pollutants usually coexist in aquatic environments. The bioaccumulation and metabolism of pollutants in aquatic organisms can be influenced by MPs. In this study, the bioaccumulation of triclosan (TCS) in tilapia tissues was determined, and metabolomics in the liver, gills, and gut were investigated after 10-day exposure to micro-sized polystyrene (PS) and TCS in water. The results showed that TCS bioaccumulated in various tissues, with the highest average concentration of 2728 ± 577 ng g-1 in the gut. The log bioaccumulation factors (BAFs) for TCS in these tissues were in the range of 0.99-3.56. Compared to the TCS treatment alone, MPs showed enhancement on the bioaccumulation of TCS in tilapia skin, liver, gut, gills, and stomach tissues in the TCS plus MP exposure. Especially in the skin and liver, the TCS concentrations were up to 2.06 and 1.38 times higher in the co-exposure of TCS and MPs, respectively. Based on the metabolomic analysis, MPs mainly disturbed the lipid and energy metabolism in tilapia fish. The altered metabolites between treatment with TCS alone and TCS + MPs were consistent, indicating that TCS has stronger disturbance in lipid and energy metabolism than MPs. This implies that the metabolism influence by the mixture of MPs and compounds is complicated in fish tissues.

Dihuang-Yinzi Alleviates Cognition Deficits via Targeting Energy-Related Metabolism in an Alzheimer Mouse Model as Demonstrated by Integration of Metabolomics and Network Pharmacology.

Energy metabolism disturbance and the consequent reactive oxygen species (ROS) overproduction play a key and pathogenic role in the onset and progression of Alzheimer’s disease (AD). Dihuang-Yinzi (DHYZ) is a traditional Chinese herbal prescription clinically applied to treat AD and other neurodegenerative diseases for a long time. However, the systematical metabolic mechanism of DHYZ against AD remains largely unclear. Here we aimed to explore the mechanism of DHYZ in the treatment of AD comprehensively in an in vivo metabolic context by performing metabolomics analysis coupled with network pharmacology study and experimental validation. The network pharmacology was applied to dig out the potential target of DHYZ against AD. The metabolomics analysis based on UPLC-HRMS was carried out to profile the urine of 2× Tg-AD mice treated with DHYZ. By integrating network pharmacology and metabolomics, we found DHYZ could ameliorate 4 key energy-related metabolic pathways, including glycerophospholipid metabolism, nicotinate/nicotinamide metabolism, glycolysis, and tricarboxylic acid cycle. Besides, we identified 5 potential anti-AD targets of DHYZ, including DAO, HIF1A, PARP1, ALDH3B2, and ACHE, and 14 key differential metabolites involved in the 4 key energy-related metabolic pathways. Furthermore, DHYZ depressed the mitochondrial dysfunction and the resultant ROS overproduction through ameliorating glycerophospholipid metabolism disturbance. Thereby DHYZ increased nicotinamide adenine dinucleotide (NAD+) content and promoted glycolysis and tricarboxylic acid (TCA) cycle, and consequently improved oxidative phosphorylation and energy metabolism. In the present study, we provided a novel, comprehensive and systematic insight into investigating the therapeutic efficacy of DHYZ against AD via ameliorating energy-related metabolism.

Gut microbiota production of trimethyl-5-aminovaleric acid reduces fatty acid oxidation and accelerates cardiac hypertrophy

Numerous studies found intestinal microbiota alterations which are thought to affect the development of various diseases through the production of gut-derived metabolites. However, the specific metabolites and their pathophysiological contribution to cardiac hypertrophy or heart failure progression still remain unclear. N,N,N-trimethyl-5-aminovaleric acid (TMAVA), derived from trimethyllysine through the gut microbiota, was elevated with gradually increased risk of cardiac mortality and transplantation in a prospective heart failure cohort (n = 1647). TMAVA treatment aggravated cardiac hypertrophy and dysfunction in high-fat diet-fed mice. Decreased fatty acid oxidation (FAO) is a hallmark of metabolic reprogramming in the diseased heart and contributes to impaired myocardial energetics and contractile dysfunction. Proteomics uncovered that TMAVA disturbed cardiac energy metabolism, leading to inhibition of FAO and myocardial lipid accumulation. TMAVA treatment altered mitochondrial ultrastructure, respiration and FAO and inhibited carnitine metabolism. Mice with γ-butyrobetaine hydroxylase (BBOX) deficiency displayed a similar cardiac hypertrophy phenotype, indicating that TMAVA functions through BBOX. Finally, exogenous carnitine supplementation reversed TMAVA induced cardiac hypertrophy. These data suggest that the gut microbiota-derived TMAVA is a key determinant for the development of cardiac hypertrophy through inhibition of carnitine synthesis and subsequent FAO.

Normalisation of diabetic heart pump function at decreased functional load.

Aim To study left ventricular (LV) hemodynamics in presence of decreased blood inflow to the heart as well as changes in myocardial content of energy metabolites in diabetic rats.Material and methods Diabetic cardiomyopathy is characterized by impaired heart contractility and by transition of cardiomyocyte energy metabolism fatty acids exclusively as a source of energy. This reduces the efficiency of energy utilization and increases the heart vulnerability to hypoxia. This study was performed on rats with type 1 diabetes mellitus induced by administration of streptozotocin (60 mg/kg). The LV pump function was studied with a catheter that allows simultaneous measurement of LV pressure and volume in each cardiac cycle.Results Blood glucose was approximately sixfold increased at 2 weeks. Heart failure was detected with decreases in ejection fraction by 27%, minute volume by 39%, and stroke work by 41%. Systolic dysfunction was based on a decrease in LV peak ejection velocity by more than 50%. Furthermore, the LV developed pressure and contractility index were within the normal range, while 1.5 times increased arterial stiffness was the factor that hampered ejection. The sum of adenine nucleotides was decreased by 21%, the ATP content was decreased by 29%, and also creatine phosphate formation was reduced in the myocardium of diabetic rats. Lactate content in the diabetic myocardium was increased almost threefold, which indicated mobilization of aerobic glycolysis. With the reduced preload, equal diastolic volume (0.3 ml), and equal blood pressure (60 mm Hg), the diabetic heart pump function did not differ from the control.Conclusion In type 1 diabetes mellitus, decreases in functional load and oxygen consumption normalize the myocardial pump function with disturbed energy metabolism.

Remifentanil reduces multiple organ and energy metabolism disturbances in a rat sepsis model.

The aim of this study was to observe the effects of remifentanil on organ damage and energy metabolism in lipopolysaccharide (LPS)-induced septic rats. A total of 45 clean-grade male Wistar rats (weight 270-320 g) were randomly divided into three groups: a control group, an LPS group, and an LPS with remifentanil treatment (LPS+REM) group. After 6 hours of modeling, the levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in lung and kidney tissues of rats in each group were detected by ELISA. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in lung and kidney tissues were determined, and the content of lactic acid, pyruvate and epinephrine in heart and kidney tissues were detected. Reverse transcription polymerase chain reaction and the Western blot test were used to detect the expression of pyruvate dehydrogenase kinase 4 (PDK4) in the myocardial tissue. We found that remifentanil treatment inhibited the levels of IL-6, TNF-α, and MDA in the lung and kidneys 6 h after the administration of LPS and increased the level of SOD activity. Treatment with remifentanil reduced the expression of lactic acid, pyruvate, and epinephrine in the heart and kidney tissues and attenuated the expression of PDK4 messenger RNA and PDK4 protein in the myocardial tissue. We concluded that remifentanil might inhibit the release of tissue inflammatory factors, regulate the body's energy metabolism, and ultimately protect the sepsis tissue damage caused by LPS.

Identification of neurodegeneration indicators and disease progression in metachromatic leukodystrophy using quantitative NMR-based urinary metabolomics.

Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by a deficiency of the arylsulfatase A (ARSA). ARSA deficiency leads to an accumulation of sulfatides primarily in the nervous system ultimately causing demyelination. With evolving therapeutic options, there is an increasing need for indicators to evaluate disease progression. Here, we report targeted metabolic urine profiling of 56 MLD patients including longitudinal sampling, using 1H (proton) nuclear magnetic resonance (NMR) spectroscopy. 1H‐NMR urine spectra of 119 MLD samples and 323 healthy controls were analyzed by an in vitro diagnostics research (IVDr) tool, covering up to 50 endogenous and 100 disease‐related metabolites on a 600‐MHz IVDr NMR spectrometer. Quantitative data reports were analyzed regarding age of onset, clinical course, and therapeutic intervention. The NMR data reveal metabolome changes consistent with a multiorgan affection in MLD patients in comparison to controls. In the MLD cohort, N‐acetylaspartate (NAA) excretion in urine is elevated. Early onset MLD forms show a different metabolic profile suggesting a metabolic shift toward ketogenesis in comparison to late onset MLD and controls. In samples of juvenile MLD patients who stabilize clinically after hematopoietic stem cell transplantation (HSCT), the macrophage activation marker neopterin is elevated. We were able to identify different metabolic patterns reflecting variable organ disturbances in MLD, including brain and energy metabolism and inflammatory processes. We suggest NAA in urine as a quantitative biomarker for neurodegeneration. Intriguingly, elevated neopterin after HSCT supports the hypothesis that competent donor macrophages are crucial for favorable outcome.

Phosphate Starvation by Energy Metabolism Disturbance in Candida albicansvip1Δ/Δ Induces Lipid Droplet Accumulation and Cell Membrane Damage.

Phosphorus in the form of phosphate (Pi) is an essential element for metabolic processes, including lipid metabolism. In yeast, the inositol polyphosphate kinase vip1 mediated synthesis of inositol heptakisphosphate (IP7) regulates the phosphate-responsive (PHO) signaling pathway, which plays an important role in response to Pi stress. The role of vip1 in Pi stress and lipid metabolism of Candida albicans has not yet been studied. We found that when vip1Δ/Δ was grown in glucose medium, if Pi was supplemented in the medium or mitochondrial Pi transporter was overexpressed in the strain, the lipid droplet (LD) content was reduced and membrane damage was alleviated. However, further studies showed that neither the addition of Pi nor the overexpression of the Pi transporter affected the energy balance of vip1Δ/Δ. In addition, the LD content of vip1Δ/Δ grown in Pi limitation medium PNMC was lower than that grown in SC, and the metabolic activity of vip1Δ/Δ grown in PNMC was also lower than that grown in SC medium. This suggests that the increase in Pi demand by a high energy metabolic rate is the cause of LD accumulation in vip1Δ/Δ. In addition, in the vip1Δ/Δ strains, the core transcription factor PHO4 in the PHO pathway was transported to the vacuole and degraded, which reduced the pathway activity. However, this does not mean that knocking out vip1 completely blocks the activation of the PHO pathway, because the LD content of vip1Δ/Δ grown in the medium with β-glycerol phosphate as the Pi source was significantly reduced. In summary, the increased Pi demand and the decreased PHO pathway activity in vip1Δ/Δ ultimately lead to LD accumulation and cell membrane damage.

Protective Effect of Trimetazidine on Potassium Ion Homeostasis in Myocardial Tissue in Mice with Heart Failure.

The occurrence of heart failure (HF) is closely correlated with the disturbance of mitochondrial energy metabolism, and trimetazidine (TMZ) has been regarded as an effective agent in treating HF. Intracellular potassium ion (K+) homeostasis, which is modulated by K+ channels and transporters, is crucial for maintaining normal myocardial function and can be disrupted by HF. This study is aimed at exploring the protective effect of TMZ on K+ homeostasis within myocardial tissue in mice with HF. We observed the pathological changes of myocardial tissue under microscopes and further measured the content of adenosine triphosphate (ATP), the activity of Na+-K+ ATPase, and the expression of ATP1α1 at the mRNA and protein levels. Moreover, we also analyzed the changes in K+ flux across the myocardial tissue in mice. As a result, we found that there was a large amount of myocardial fiber lysis and fracture in HF myocardial tissue. Meanwhile, the potassium flux of mice with HF was reduced, and the expression of ATP1α1, the activity of Na+-K+ ATPase, and the supply and delivery of ATP were also decreased. In contrast, TMZ can effectively treat HF by restoring K+ homeostasis in the local microenvironment of myocardial tissues.

Evidence of Energy Metabolism Alterations in Cultured Neonatal Astrocytes Derived from the Ts65Dn Mouse Model of Down Syndrome.

For many decades, neurons have been the central focus of studies on the mechanisms underlying the neurodevelopmental and neurodegenerative aspects of Down syndrome (DS). Astrocytes, which were once thought to have only a passive role, are now recognized as active participants of a variety of essential physiological processes in the brain. Alterations in their physiological function have, thus, been increasingly acknowledged as likely initiators of or contributors to the pathogenesis of many nervous system disorders and diseases. In this study, we carried out a series of real-time measurements of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in hippocampal astrocytes derived from neonatal Ts65Dn and euploid control mice using a Seahorse XFp Flux Analyzer. Our results revealed a significant basal OCR increase in neonatal Ts65Dn astrocytes compared with those from control mice, indicating increased oxidative phosphorylation. ECAR did not differ between the groups. Given the importance of astrocytes in brain metabolic function and the linkage between astrocytic and neuronal energy metabolism, these data provide evidence against a pure “neurocentric” vision of DS pathophysiology and support further investigations on the potential contribution of disturbances in astrocytic energy metabolism to cognitive deficits and neurodegeneration associated with DS.

СОСТОЯНИЕ АДРЕНОКОРТИКАЛЬНОЙ И СИМПАТОАДРЕНАЛОВОЙ СИСТЕМ, СУБСТРАТОВ ЭНЕРГЕТИЧЕСКОГО ОБМЕНА В КРОВИ ЧЕЛОВЕКА ПРИ ГОДИЧНОМ ПРЕБЫВАНИИ В УСЛОВИЯХ ГИПОБАРИЧЕСКОЙ ГИПОКСИИ, ГИПОКИНЕЗИИ И ИЗОЛЯЦИИ

Year-long life on Antarctic scientific station Vostok was characterized by exposure to the physiologically important factors including hypobaric hypoxia (Р = 460 mm Hg) due to the location on the Central Ice Sheet, hypokinesia due to staying indoor most of the time because of very low temperatures outdoors, physical and social isolation from the world. The paper attempts to define which of these factors determined the human body stress-reaction and energy metabolism. Venous plasma samples were periodically gathered for analysis from 16 members of the 13th Soviet Antarctic expedition to the station Vostok in 1968. Members of the expedition were divided into 2 groups. One group was experimental, i.e. intermittently consumed anti-asthenia amino acid and vitamin supplements and psychoactive drugs, and the other was the placebo control. The investigation showed that in the course of the year-long existence in the extreme environment the averaged levels of 11-oxicorticosteroids and adrenergic compounds were elevated while the noradrenergic levels were at the bottom margins of their normal ranges. Averaged values of blood glucose and total cholesterol were well within the range of normal variations. Anti-asthenia supplements mitigated the chronic stress and did not disturb energy metabolism.

Energy metabolism homeostasis in cardiovascular diseases.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the general population. Energy metabolism disturbance is one of the early abnormalities in CVDs, such as coronary heart disease, diabetic cardiomyopathy, and heart failure. To explore the role of myocardial energy homeostasis disturbance in CVDs, it is important to understand myocardial metabolism in the normal heart and their function in the complex pathophysiology of CVDs. In this article, we summarized lipid metabolism/lipotoxicity and glucose metabolism/insulin resistance in the heart, focused on the metabolic regulation during neonatal and ageing heart, proposed potential metabolic mechanisms for cardiac regeneration and degeneration. We provided an overview of emerging molecular network among cardiac proliferation, regeneration, and metabolic disturbance. These novel targets promise a new era for the treatment of CVDs.

IKKε protects against starvation-induced NLRP3 inflammasome and pyroptosis in H9c2 cells by alleviating mitochondrial injury

The deprivation of myocardial nutrition causes cardiomyocyte death and disturbance of energy metabolism. IKKε plays an important regulatory role in many biological events such as inflammation, redox reaction, cell death, etc. However, the more in-depth mechanism by which IKKε contributes to cardiomyocytes death in nutrition deprivation remains poorly understood. IKKε expression was knocked down by siRNA in H9c2 cells, and cells were cultured under starvation conditions to simulate ischemic conditions. Starvation triggered greater NLRP3 activation, accompanied by more IL-1β, IL-18 and caspase-1 release in the siIKKε H9c2 cells compared with the control H9c2 cells. Western blot and immunofluorescence showed that the IKKε konckdown promoted NLRP3 expressions and ROS release under starvation conditions. Furthermore, electron micrography and JC-1 analysis revealed that IKKε konckdown resulted in aggravated mitochondrial damage and more mitochondrial ROS (mtROS) released in vitro. Notably, Western blot analysis showed that IKKε deficiency activated the TBK1 and IRF3 signaling pathways to promote pyroptosis in vitro. Collectively, our results indicate that IKKε protects against cardiomyocyte injury by reducing mitochondrial damage and NLRP3 expression following nutrition deprivation via regulation of the TBK1/IRF3 signaling pathway. This study further revealed the mechanism of IKKε in inflammation and myocardial nutrition deprivation.

Evaluation of immune stimulatory products for whiteleg shrimp (Penaeus vannamei) by a metabolomics approach

The use of probiotics, prebiotics and dietary fiber has become a common practice in shrimp aquaculture as alternatives to antibiotic treatment. However, not much is known about the metabolic mechanisms underlying the effects of probiotics and immunostimulant used in shrimp aquaculture. In this study, a gas chromatography−mass spectrometry (GC−MS) based metabolomics approach was used to characterize metabolite profiles of haemolymph and gills of whiteleg shrimp (Penaeus vannamei) exposed to four treatments (cellulose fiber, probiotics with Vibrio alginolyticus, a combination of cellulose fiber and V. alginolyticus and a control treatment). The cellulose fiber was administrated as a feed additive (100 mg⋅Kg−1 feed), while the probiotics was applied in the water (105 UFC⋅mL−1 culture water). The results showed significant differences in haemolymph metabolite profiles of immune stimulated treatments compared to the control and among treatments. The combination of cellulose fiber and probiotics resulted in greater differences in metabolic profiles, suggesting a better immune stimulation with this approach. The changes in haemolymph metabolome of treated shrimp reflected several biochemical pathway modifications, including changes in amino acid and fatty acid metabolism, disturbances in energy metabolism and antimicrobial activity and stress responses. For gill tissues, significant differences were only found in lactic acid between the probiotic group and the control. Among the altered metabolites, the increases of itaconic acid in haemolymph, and lactic acid in both haemolymph and gill tissues of immune-stimulated suggest the potential use of these metabolites as biomarkers for health assessment in aquaculture.

A Novel Insight Into the Fate of Cardiomyocytes in Ischemia-Reperfusion Injury: From Iron Metabolism to Ferroptosis.

Ischemia-reperfusion injury (IRI), critically involved in the pathology of reperfusion therapy for myocardial infarction, is closely related to oxidative stress the inflammatory response, and disturbances in energy metabolism. Emerging evidence shows that metabolic imbalances of iron participate in the pathophysiological process of cardiomyocyte IRI [also termed as myocardial ischemia-reperfusion injury (MIRI)]. Iron is an essential mineral required for vital physiological functions, including cellular respiration, lipid and oxygen metabolism, and protein synthesis. Nevertheless, cardiomyocyte homeostasis and viability are inclined to be jeopardized by iron-induced toxicity under pathological conditions, which is defined as ferroptosis. Upon the occurrence of IRI, excessive iron is transported into cells that drive cardiomyocytes more vulnerable to ferroptosis by the accumulation of reactive oxygen species (ROS) through Fenton reaction and Haber–Weiss reaction. The increased ROS production in ferroptosis correspondingly leads cardiomyocytes to become more sensitive to oxidative stress under the exposure of excess iron. Therefore, ferroptosis might play an important role in the pathogenic progression of MIRI, and precisely targeting ferroptosis mechanisms may be a promising therapeutic option to revert myocardial remodeling. Notably, targeting inhibitors are expected to prevent MIRI deterioration by suppressing cardiomyocyte ferroptosis. Here, we review the pathophysiological alterations from iron homeostasis to ferroptosis together with potential pathways regarding ferroptosis secondary to cardiovascular IRI. We also provide a comprehensive analysis of ferroptosis inhibitors and initiators, as well as regulatory genes involved in the setting of MIRI.

Antitrypanosomal Activity of Anthriscus Nemorosa Essential Oils and Combinations of Their Main Constituents.

This study aimed to investigate the susceptibility of Trypanosoma brucei to the Anthriscus nemorosa essential oils (EOs), isolated compounds from these oils, and artificial mixtures of the isolated compounds in their conventional and nanoencapsulated forms. The chemical composition of the essential oils from the aerial parts and roots of Anthriscus nemorosa, obtained from a wild population growing in central Italy, were analyzed by gas chromatography/mass spectrometry (GC/MS). In both cases, the predominant class of compounds was monoterpene hydrocarbons, which were more abundant in the EOs from the roots (81.5%) than the aerial parts (74.0%). The overall results of this work have shed light on the biological properties of A. nemorosa EO from aerial parts (EC50 = 1.17 μg/mL), farnesene (EC50 = 0.84 μg/mL), and artificial mixtures (Mix 3–5, EC50 in the range of 1.27 to 1.58 μg/mL) as relevant sources of antiprotozoal substances. Furthermore, the pool measurements of ADP (adenosine diphosphate) and NTPs (nucleoside triphosphates) in the cultivated bloodstream form of trypanosomes exposed to different concentrations of EOs showed a disturbed energy metabolism, as indicated by increased pools of ADP in comparison to ATP (adenosine triphosphate) and other NTPs. Ultimately, this study highlights the significant efficacy of A. nemorosa EO to develop long-lasting and effective antiprotozoal formulations, including nanoemulsions.

Transcription Factor E2F1 Knockout Promotes Mice White Adipose Tissue Browning Through Autophagy Inhibition.

Obesity is associated with energy metabolic disturbance and is caused by long-term excessive energy storage in white adipose tissue (WAT). The WAT browning potentially reduces excessive energy accumulation, contributing an attractive target to combat obesity. As a pivotal regulator of cell growth, the transcription factor E2F1 activity dysregulation leads to metabolic complications. The regulatory effect and underlying mechanism of E2F1 knockout on WAT browning, have not been fully elucidated. To address this issue, in this study, the in vivo adipose morphology, mitochondria quantities, uncoupling protein 1 (UCP-1), autophagy-related genes in WAT of wild-type (WT) and E2F1–/– mice were detected. Furthermore, we evaluated the UCP-1, and autophagy-related gene expression in WT and E2F1–/– adipocyte in vitro. The results demonstrated that E2F1 knockout could increase mitochondria and UCP-1 expression in WAT through autophagy suppression in mice, thus promoting WAT browning. Besides, adipocytes lacking E2F1 showed upregulated UCP-1 and downregulated autophagy-related genes expression in vitro. These results verified that E2F1 knockout exerted effects on inducing mice WAT browning through autophagy inhibition in vivo and in vitro. These findings regarding the molecular mechanism of E2F1-modulated autophagy in controlling WAT plasticity, provide a novel insight into the functional network with the potential therapeutic application against obesity.

RF Coil Setup for 31P MRSI in Tongue Cancer in vivo at 7 T.

Surgery for tongue cancer often results in a major loss in quality of life. While MRI may be used to minimise the volume of excised tissue, often the full tumour extent is missed. This tumour extent may be detected with metabolic imaging. One of the main reasons for the lack of metabolic information on tongue cancer would be the absence of an x-nuclear coil with the tongue as a focus target. Metabolic MRI through 31P MRSI is known as a powerful tool to non-invasively study elevated cell proliferation and disturbed energy metabolism in tumours. Severe magnetic field non-uniformities are inherently caused by the substantial difference in magnetic susceptibilities of tissue and air in the mouth and its environs. Despite this, the wide chemical shift dispersion of 31P could still facilitate precise detection of the cell proliferation biomarkers, phospomonoesters and diesters, as well as energy metabolites ATP, inorganic phosphate, and phosphocreatine potentially mapped over the tongue or tumour in vivo. In this study, we present the first 31P MRSI data of the human tongue in vivo from healthy volunteers and a patient with a tongue tumour at 7 T MRI using a 1H 8-channel transceiver setup placed inside a body 31P transmitter, which is able to get a uniform excitation from the tongue while providing comfortable access to the patient. In addition, a user-friendly external 31P receiver array is used to provide high sensitivity (80%) comparable to an uncomfortable inner mouth loop coil positioned on the tongue. The primary aim is the demonstration of 31P metabolite profiles in the tongue and the differences between healthy and malignant tissue. Indeed, clear elevated cell proliferation expressed as enhanced phosphomonoesters is observed in the tumour vs. the healthy part of the tongue. This can be performed within a total scan duration of 30 min, comparable to clinical scans, with a spatial resolution of 1.5 cm for the 10-min 31P MRSI scan.

Effect of hydro-alcoholic extract of centella asiatica on streptozotocin induced memory dysfunction in adult zebrafish

• Hydro-alcoholic extract of centella asiatica ameliorates streptozotocin induced memory dysfunction by decreasing the level of AChEs. • The neuroprotective effect of hydro-alcoholic extract of CA is due to its antioxidant and memory enhancing activity. • Hydro-alcoholic extract of CA improved memory function which was assessed by behavioural parameters (T-maze test and light and dark test). • Hydro-alcoholic extract of CA attenuates oxidative stress by decreasing LPO level in the adult zebrafish. Streptozotocin (STZ) causes learning and memory impairment in adult zebrafish by causing the disturbance in glucose and energy metabolism of the brain. Hydro-alcoholic extract of centella asiatica (HA-CA) has been demonstrated to improve cognitive functions due to its antioxidant property. In this study, adult zebrafish (approx 3 months old, weight range from 470–530 mg) was subjected to the STZ administration (300 mg/kg; i.p ) followed by drug treatment with HA-CA (10 and 20 μg/mL) before 24 h of STZ administration followed by blood glucose level measurement, behavioral parameters (light and dark test and T-maze test) and biochemical parameters (protein estimation, LPO and AChEs activity). Exposure to STZ in adult zebrafish showed significant alterations in behavioural and biochemical analysis. In the light-dark test STZ treated zebrafish shown their preference in dark compartment as compared to normal group and in T-maze test STZ treated zebrafish has shown more time spent in the unfavorable zone with an increase in total latency (TL) as compared to the normal group. However, drug administration with CA (10 and 20 μg/mL) significantly improved the memory deficits in both light and dark test and T-maze test as compared to the STZ treated group which indicated improved memory function with a significant decrease in oxidative stress level (decrease LPO) and AChEs activity. HA- CA markedly improved memory functions in adult zebrafish due to its anti-oxidant potential.

Intracranial Pressure Variability: A New Potential Metric of Cerebral Ischemia and Energy Metabolic Dysfunction in Aneurysmal Subarachnoid Hemorrhage?

It was recently reported that lower intracranial pressure variability (ICPV) is associated with delayed ischemic neurological deficits and unfavorable outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to determine whether lower ICPV also correlated with worse cerebral energy metabolism after aSAH. A total of 75 aSAH patients treated in the neurointensive care unit at Uppsala University Hospital, Sweden between 2008 and 2018 and with both intracranial pressure and cerebral microdialysis (MD) monitoring during the first 10 days after ictus were included in this retrospective study. ICPV was calculated with a bandpass filter limited to intracranial pressure slow waves with a wavelength of 55 to 15 seconds. Cerebral energy metabolites were measured hourly with MD. The monitoring period was divided into 3 phases; early (days 1 to 3), early vasospasm (days 4 to 6.5), and late vasospasm (days 6.5 to 10). Lower ICPV was associated with lower MD-glucose in the late vasospasm phase, lower MD-pyruvate in the early vasospasm phases, and higher MD-lactate-pyruvate ratio (LPR) in the early and late vasospasm phases. Lower ICPV was associated with poor cerebral substrate supply (LPR >25 and pyruvate <120 µM) rather than mitochondrial failure (LPR >25 and pyruvate >120 µM). There was no association between ICPV and delayed ischemic neurological deficit, but lower ICPV in both vasospasm phases correlated with unfavorable outcomes. Lower ICPV was associated with an increased risk for disturbed cerebral energy metabolism and worse clinical outcomes in aSAH patients, possibly explained by a vasospasm-related decrease in cerebral blood volume dynamics and cerebral ischemia.

Time-ordered dysregulated ceRNA networks reveal disease progression and diagnostic biomarkers in ischemic and dilated cardiomyopathy

Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are the two main causes of heart failure (HF). Despite similar clinical characteristics and common “HF pathways”, ICM and DCM are expected to have different personalized treatment strategies. The underlying mechanisms of ICM and DCM have yet to be fully elucidated. The present study developed a novel computational method for identifying dysregulated long noncoding RNA (lncRNA)–microRNA (miRNA)–mRNA competing endogenous RNA (ceRNA) triplets. Time-ordered dysregulated ceRNA networks were subsequently constructed to reveal the possible disease progression of ICM and DCM based on the method. Biological functional analysis indicated that ICM and DCM had similar features during myocardial remodeling, whereas their characteristics differed during progression. Specifically, disturbance of myocardial energy metabolism may be the main characteristic during DCM progression, whereas early inflammation and response to oxygen are the characteristics that may be specific to ICM. In addition, several panels of diagnostic biomarkers for differentiating non-heart failure (NF) and ICM (NF-ICM), NF-DCM, and ICM-DCM were identified. Our study reveals biological differences during ICM and DCM progression and provides potential diagnostic biomarkers for ICM and DCM.