Glycogen Phosphorylase Isoenzyme Research Articles

Computational insights into novel inhibitor indole-heterocycle specific against glycogen phosphorylase isoenzymes interaction mechanism.

Background: Glycogen phosphorylase (GP) is a potential drug target. As the three subtypes of GP are highly conserved, it is difficult to research their specificity. However, compound 1 inhibits the GP subtypes differently and was studied to aid in designing specific inhibitors. Results: Molecular docking showed that the ligands in GP subtype complexes had some differences in spatial conformation and binding modes, stabilized by polar and nonpolar interactions. The results were confirmed through kinetic experiments, with affinities of -85.230 (brain GP), -73.809 (liver GP) and -66.061kJ/mol (muscle GP). Conclusion: The study provides insight into the possible reasons for differences in compound 1's inhibitory activity against the GP subtypes and offers guidance in designing target molecules for regulating selectivity among the subtypes.

Glycogen phosphorylase isoenzyme GPbb versus GPmm regulation of ventromedial hypothalamic nucleus glucoregulatory neurotransmitter and counter-regulatory hormone profiles during hypoglycemia: Role of L-lactate and octadecaneuropeptide

Glucose accesses the brain primarily via the astrocyte cell compartment, where it passes through the glycogen shunt before catabolism to the oxidizable fuel L-lactate. Glycogen phosphorylase (GP) isoenzymes GPbb and GPmm impose distinctive control of ventromedial hypothalamic nucleus (VMN) glucose-regulatory neurotransmission during hypoglycemia, but lactate and/or gliotransmitter involvement in those actions is unknown. Lactate or the octadecaneuropeptide receptor antagonist cyclo(1–8)[DLeu5] OP (LV-1075) did not affect gene product down-regulation caused by GPbb or GPmm siRNA, but suppressed non-targeted GP variant expression in a VMN region-specific manner. Hypoglycemic up-regulation of neuronal nitric oxide synthase was enhanced in rostral and caudal VMN by GPbb knockdown, yet attenuated by GPMM siRNA in the middle VMN; lactate or LV-1075 reversed these silencing effects. Hypoglycemic inhibition of glutamate decarboxylase65/67 was magnified by GPbb (middle and caudal VMN) or GPmm (middle VMN) knockdown, responses that were negated by lactate or LV-1075. GPbb or GPmm siRNA enlarged hypoglycemic VMN glycogen profiles in rostral and middle VMN. Lactate and LV-1075 elicited progressive rostral VMN glycogen augmentation in GPbb knockdown rats, but stepwise-diminution of rostral and middle VMN glycogen after GPmm silencing. GPbb, not GPmm, knockdown caused lactate or LV-1075 – reversible amplification of hypoglycemic hyperglucagonemia and hypercorticosteronemia. Results show that lactate and octadecaneuropeptide exert opposing control of GPbb protein in distinct VMN regions, while the latter stimulates GPmm. During hypoglycemia, GPbb and GPmm may respectively diminish (rostral, caudal VMN) or enhance (middle VMN) nitrergic transmission and each oppose GABAergic signaling (middle VMN) by lactate- and octadecaneuropeptide-dependent mechanisms.

Scale-Invariant Feature Transform (SIFT) Algorithm-Based Detection of Cardiac Insufficiency in Sepsis Patients with Echocardiography

This research aimed to explore the application of cardiac ultrasound imaging (CUI) in the examination and diagnosis of sepsis patients with cardiac insufficiency under a speckle tracking algorithm (STA). Scale-invariant feature transform (SIFT) algorithm was introduced to process images of CUI through STA under feature points of cardiac ultrasonic images. 90 patients with sepsis who were admitted to the hospital were selected and randomly divided into a sound cardiac function group (n = 62) (group A) and a cardiac insufficient group (n = 28) (group B) under whether they had cardiac insufficiency, and 20 healthy people were selected as a control group. Sepsis patients were examined on the seventh day after diagnosis including laboratory-related indicators, echocardiography, and echocardiographic data. The results showed that there were differences in cardiac ultrasound, cardiac marker, and laboratory examinations of subjects in the three groups ( P < 0.05). Creatine kinase isoenzyme-MB (CK-MB), glycogen phosphorylase isoenzyme BB (GPBB), and heart-type fatty acid-binding protein (H-FABP) of subjects in the three groups showed statistically marked differences ( P < 0.05). The other results indicated tricuspid late diastolic blood flow velocity (A′) value was greater than stroke volume (SV) and isovolumetric relaxation time (IVRT) value, followed by left ventricular ejection fraction (EF) and cardiac output per minute output (CO), and EF and CO values were over peak velocity of right ventricular free wall tricuspid valve systolic movement (SM) and left ventricular fractional shortening (FS) value, and left ventricular end-diastolic volume (EDV) value came next. The analysis of CUI based on STA could help doctors to judge sepsis patients with cardiac function. In addition, sepsis patients with sound cardiac function and sepsis patients with cardiac insufficiency could be distinguished by CUI, which had certain guiding significance for clinical diagnosis.

The Diagnostic Value of Plasma miRNA-497, cTnI, FABP3 and GPBB in Pediatric Sepsis Complicated with Myocardial Injury.

ObjectiveTo investigate the diagnostic value of plasma miRNA-497, cardiac troponin I (cTnI), fatty acid binding protein 3 (FABP3), glycogen phosphorylase isoenzyme BB (GPBB) in pediatric sepsis complicated with myocardial injury.MethodsFrom August 2018 to February 2020, 82 children with sepsis admitted to our hospital and 50 health children who came for physical examination (defined as control group) were enrolled in this study. Children with sepsis and myocardial injury were enrolled in the combined group (n=35), and those without myocardial injury were enrolled in the sepsis group (n=47). General data of three groups were collected, and the levels of miRNA-497, FABP3, GPBB, creatine kinase isoenzyme MB (CK-MB), procalcitonin (PCT), C-reactive protein (CRP), cTnI and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were detected and the cardiac function was measured. The diagnostic value of plasma miRNA-497, cTnI, FABP3 and GPBB in pediatric sepsis complicated with myocardial injury was analyzed.ResultsThe infection site of the combined group was not significantly different from that of the sepsis group. The levels of miRNA-497, FABP3, GPBB, CK-MB, PCT, CRP, cTnI, NT-proBNP in the combined group were all higher than those in the sepsis group and the control group (P<0.05), and the left ventricular ejection fraction (LVEF) in the combined group was significantly lower than that in the other two group (P<0.05). The area under the curve (AUC) of the combination of miRNA-497, FABP3, GPBB, and cTnI in the diagnosis of sepsis complicated with myocardial injury was significantly higher than that of CK-MB, PCT, CRP, NT-proBNP alone (P<0.05), but there was no significant difference when compared with miRNA-497, FABP3, GPBB and cTnI alone (P>0.05). When the optimal thresholds of miRNA-497, FABP3, GPBB, and cTnI were set to 2.03, 6.23ng/mL, 4.01ng/mL, 1.23ng/mL, respectively, the sensitivity was 95.65%, 88.89%, 82.61%, 87.50%, respectively; the specificity was 83.33%, 94.12%, 83.33%, 90.91%, respectively; and the accuracy was 91.43%, 91.43%, 82.86%, 88.57%, respectively. Pearson correlation analysis indicating that miRNA-497 was positively correlated with the levels of FABP3, GPBB, and cTnI in the combined group (r=0.821, 0.621, 0.782, P<0.05).ConclusionPlasma miRNA-497, cTnI, FABP3, and GPBB levels were increased in pediatric sepsis complicated with myocardial injury, and their combination had high diagnostic value, which was of great clinical significance for early diagnosis and early treatment of pediatric sepsis complicated with myocardial injury.

Nimbolide prevents myocardial damage by regulating cardiac biomarkers, antioxidantlevel, and apoptosis signaling against doxorubicin-induced cardiotoxicity in rats.

The current work planned to assess the protecting properties of nimbolide against doxorubicin (DOX)-treated myocardial damage. Myocardial damage was produced with2.5 mg/kg of DOX given onalternative days (14 days). Thiobarbituric acid reactive substances (TBARS) levels of alipid peroxidative marker were elevated, whereas reduced body weight, heart weight, blood pressure indices and reduced levels of antioxidants like glutathione-S-transferase, superoxide dismutase, catalase, glutathione peroxidase, glutathione, and glutathione reductase were observed in the heart tissue of DOX-treated animals. DOX-treated animalsshowedaugmented levels of cardiac markers likes monocyte chemotactic protein-1, interferon-gamma, aspartate transferase, creatine kinase, lactate dehydrogenase, creatine kinase-muscle/brain, heart-type fatty acid-binding protein, glycogen phosphorylase isoenzyme BB, transforming growth factor-β, brain natriuretic peptide, myoglobin, and cTnI in serum. Histopathological assessment confirmed the DOX-induced cardiotoxicity. Furthermore, DOX-induced rats showed augmented inflammatory mediators (nuclear factor-κB [NF-kB], tumor necrosis factor-α [TNF-α], and interleukin-1β [IL-1β]) and increased PI3K/Akt signaling proteins (PI3K, p-Bad/Bad, caspase-3, and p-Akt), whereas decreased oxidative markers (HO-1 and NQO-1) and p-PTEN were observed. Nimbolide-supplemented rats showed reduced activity/levels of cardiac markers and TBARS levels in serum and heart tissue. Levels of enzymatic and nonenzymatic antioxidants were augmented in the heart tissue of nimbolide-supplemented rats. Nimbolide influence decreased apoptosis, inflammation, and enhanced antioxidant markers through the modulation of p-Bad/Bad, caspase-3, PI3K, p-Akt, TNF-α, NF-kB, IL-1β, HO-1, NQO-1, and p-PTEN markers. The histopathological explanations were observed to be in line with biochemical analysis. Therefore, the findingof current work wasthat nimbolide has a defensiveeffect onthe myocardium against DOX-induced cardiac tissue damage.

Results of an open label feasibility study of sodium valproate in people with McArdle disease

McArdle disease results from a lack of muscle glycogen phosphorylase in skeletal muscle tissue. Regenerating skeletal muscle fibres can express the brain glycogen phosphorylase isoenzyme. Stimulating expression of this enzyme could be a therapeutic strategy. Animal model studies indicate that sodium valproate (VPA) can increase expression of phosphorylase in skeletal muscle affected with McArdle disease. This study was designed to assess whether VPA can modify expression of brain phosphorylase isoenzyme in people with McArdle disease. This phase II, open label, feasibility pilot study to assess efficacy of six months treatment with VPA (20 mg/kg/day) included 16 people with McArdle disease. Primary outcome assessed changes in VO2peak during an incremental cycle test. Secondary outcomes included: phosphorylase enzyme expression in post-treatment muscle biopsy, total distance walked in 12 min, plasma lactate change (forearm exercise test) and quality of life (SF36). Safety parameters. 14 participants completed the trial, VPA treatment was well tolerated; weight gain was the most frequently reported drug-related adverse event. There was no clinically meaningful change in any of the primary or secondary outcome measures including: VO2peak, 12 min walk test and muscle biopsy to look for a change in the number of phosphorylase positive fibres between baseline and 6 months of treatment. Although this was a small open label feasibility study, it suggests that a larger randomised controlled study of VPA, may not be worthwhile.

MODERN METHODS TO DIFFERENTIATE BETWEEN CHEST PAIN AND CARDIAC ISCHEMIA

Acute coronary syndrome (ACS) is a group of conditions which often present with similar signs and symptoms while having different outcomes and complications. Therefore it is essential to differentiate between them as soon as possible and provide appropriate management. Acute coronary syndromes are classified into two categories: STE-ACS (ST segment Elevation Acute Coronary Syndrome) and NSTE-ACS (Non ST segment Elevation Acute Coronary Syndrome). STE-ACS stands for ST Elevation Acute Coronary Syndrome all of which demonstrate significant ST elevations on ECG due to complete blockage of artery by thrombus, while NSTE-ACS is due to partial occlusion of artery which exhibit ST segment depression and/or T wave inversions. Patients with NSTE-ACS who do not develop infarction are diagnosed with unstable angina, which itself is a precursor of myocardial infarction. Acute coronary syndromes are considered multifactorial and risk factors most commonly associated with development of acute coronary syndromes include: hypertension, smoking, diabetes, obesity, sedentary life-style, hereditary conditions etc. Chronic stress to the coronary endothelium eventually leads to inflammation and atherosclerotic plaque formation. Plaque at some point with additional stress will rupture and trigger thrombus formation. Probability of plaque rupture depends on its composition: stable plaques contain small fatty core and thick fibrous cap, unstable plaque have larger fatty cores and thin fibrous cap. Patients with acute coronary syndromes present with chest pain and/or discomfort and may experience tightness and pressure sensation; pain may radiate to left or both arms, jaw, back or stomach, sweating, dyspnea and dizziness are also common complaints. Whenever we suspect ACS first diagnostic tests is always ECG (Electrocardiography). If ST segment is persistently elevated STEMI (ST Elevation Myocardial Infarction) can be diagnosed and reperfusion therapy is indicated; but if ST segment is depressed and/or T wave inversion is present laboratory tests are necessary for diagnosis. Cardiac biomarkers mainly used in the clinic are Troponins and CK-MB (Creatine Kinase MB), yet LDH (lactate dehydrogenase), B-type natriuretic peptide and C-reactive protein can be used additionally. Several studies have been conducted in hopes to find other myocardial markers useful for diagnosis of ACS, one of which tested candidate biomarkers such as hFABP (Heart-type fatty acid binding protein), GPBB (Glycogen Phosphorylase Isoenzyme BB), S100, PAPP-A (Pregnancy-associated plasma protein A), TNF (Tumor Necrosis Factor), IL6 (Interleukin 6), IL18 (Interleukin 18), CD40 (Cluster of differentiation 40) ligand, MPO (Myeloperoxidase), MMP9 (Matrix metallopeptidase 9), cell-adhesion molecules, oxidized LDL (Low Density Lipoprotein), glutathione, homocysteine, fibrinogen, and D-dimer, procalcitonin. The idea of this study was to estimate usefulness of combining enzymatic markers with nonenzymatic ones in the clinical settings.

Novel Invasive and Noninvasive Cardiac-Specific Biomarkers in Obesity and Cardiovascular Diseases.

Cardiovascular disease (CVD) is the leading cause of fatality and disability worldwide regardless of gender. Obesity has reached epidemic proportions in population across different regions. According to epidemiological studies, CVD risk markers in childhood obesity are one of the significant risk factors for adulthood CVD, but have received disproportionally little attention. This review has examined the evidence for the presence of traditional cardiac biomarkers (nonspecific; lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, creatine kinase, myoglobulin, glycogen phosphorylase isoenzyme BB, myosin light chains, ST2, and ischemia-modified albumin) and novel emerging cardiac-specific biomarkers (cardiac troponins, natriuretic peptides, heart-type fatty acid-binding protein, and miRNAs). Besides, noninvasive anatomical and electrophysiological markers (carotid intima-media thickness, coronary artery calcification, and heart rate variability) in CVDs and obesity are also discussed. Modifiable and nonmodifiable risk factors associated with metabolic syndrome in the progression of CVD, such as obesity, diabetes, hypertension, dyslipidemia, oxidative stress, inflammation, and adipocytokines are also outlined. These underlying prognostic risk factors predict the onset of future microvascular and macrovascular complications. The understanding of invasive and noninvasive cardiac-specific biomarkers and the risk factors may yield valuable insights into the pathophysiology and prevention of CVD in a high-risk obese population at an early stage.

Markers of maternal cardiac dysfunction in pre-eclampsia and superimposed pre-eclampsia

AuthorsFrances Conti-Ramsden MBBS Academic Clinical Fellow1, Carolyn Gill PhD BRC Research Assistant1, Paul T Seed MSc CStat Senior Lecturer in Medical Statistics1, Kate Bramham PhD Clinical Senior Lecturer in Nephrology2, Lucy C Chappell PhD NIHR Research Professor in Obstetrics1, Fergus P McCarthy PhD Clinical Senior Lecturer in Obstetrics and Gynaecology1,3. ObjectivesTo determine whether glycogen phosphorylase isoenzyme B (GPBB) and/or brain natriuretic peptide (BNP) concentrations are elevated in pre-eclampsia and superimposed pre-eclampsia (SPE), demonstrating cardiac ischaemia and strain. Study designA nested case-control study was performed using samples and clinical data available from a prospective pregnancy cohort. Four groups were selected: healthy pregnant controls (n = 21), pre-eclampsia (n = 19), pre-existing chronic hypertension (CHT) and/or chronic kidney disease (CKD) without (n = 20) or with superimposed pre-eclampsia (SPE) (n = 19). Plasma samples were taken at time of disease or the third trimester in controls. Main outcome measuresPlasma concentrations of GPBB and BNP. ResultsThere was no significant difference in GPBB plasma concentrations between controls and pre-eclampsia (geometric mean (GM) [95% CI]: 4.74 [2.54–8.84]ng/mL vs 5.01 [2.58–9.74]ng/mL, p = 0.90)), or between CHT and/or CKD and SPE (GM [95% CI]: 9.49 [4.93–18.25]ng/mL vs 10.24 [5.27–19.92]ng/mL, p = 0.87). BNP plasma concentrations were significantly raised in women with pre-eclampsia compared to controls (GM [95% CI]: 31.83 [20.18–50.22]pg/mL vs 11.33 [7.34–17.51]pg/mL, p = 0.001). Women with CKD, but not CHT, who developed SPE had elevated BNP concentrations. There were no significant differences in BNP concentration between women with comorbidity (CHT and/or CKD) and controls. ConclusionsGPBB has a limited role as a biomarker in hypertensive disorders of pregnancy. BNP concentrations were elevated in pre-eclampsia compared to controls. This suggests cardiac strain at the time of pre-eclampsia. Further studies are needed to examine whether BNP can identify women at increased risk of cardiovascular disease.

Paper microfluidic device for early diagnosis and prognosis of acute myocardial infarction via quantitative multiplex cardiac biomarker detection

The early detection of acute myocardial infarction (AMI) upon the onset of chest pain symptoms is crucial for patient survival. However, this detection is challenging, particularly without a persistent elevation of ST-segment reflected in an electrocardiogram or in blood tests. A majority of the available point-of-care testing devices allow accurate and rapid diagnosis of AMI. However, AMI diagnosis is reliable only at intermediate and later stages, with myocardial injury (> 6 h) and MI, based on the expression of specific cardiac biomarkers including troponin I or T (cTnI or cTnT), creatine kinase-MB (CK−MB), and myoglobin. Diagnosis at the early myocardial ischemia stage is not possible. To overcome this limitation, a sensitive and rapid microfluidic paper-based device (µPAD) was developed for the simultaneous detection of multiple cardiac biomarkers for the early and late diagnosis of AMI. The glycogen phosphorylase isoenzyme BB (GPBB) was detected during early (within first 4 h) ischemic myocardial injury. On the same µPAD platform, detection of prolonged elevation of levels of cTnT and CK-MB, which are only produced 6 h after the onset of chest pain in human serum, was possible. Sandwich immunoassay performed on the µPAD achieved reproducibility (RSD approximately 10% and intra-and inter-day precision (CV 10–20%, 99th percentile), as well as consistently stable test results for 28 days, with strong correlation (r2= 0.962), using the standard Siemens Centaur XPT Immunoassay system. The present findings indicate the potential of the µPAD platform as a point-of-care device for the early diagnosis and prognosis of AMI.

Glycogen Phosphorylase Isoenzyme Bb, Myoglobin and BNP in ANT-Induced Cardiotoxicity

Anthracyline (ANT) has been demonstrated as a useful treatment for leukemia and solid tumors. However, ANT has previously reported cardiotoxic effects, which can reduce the therapeutic index for cancer treatment. This study aimed to investigate the associations of glycogen phosphorylase isoenzyme BB (GPBB), myoglobin (Mb), and brain natriuretic peptide (BNP) with anthracycline (ANT-induced cardiotoxicity (AIC)) amongst the Chinese population. Patients suffering from leukemia were recruited. Electrocardiogram and echocardiography were used along with chemotherapy to determine left ventricular ejection fraction (LVEF), mitral ratio of peak early to late diastolic filling velocity (E/A), E-wave deceleration time (EDT), and isovolumic relaxation time (IVRT). Double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) was employed to examine and compare serum GPBB, Mb, and BNP levels. Following chemotherapy, the patients presented higher levels of serum GPBB, Mb, and BNP than before chemotherapy treatment. The levels of LVEF (%), E/A, and IVRT were significantly decreased after chemotherapy, while EDT was markedly increased. The cumulative ANT dose was positively corelated to serum GPBB, Mb, and BNP levels while it was negatively corelated to LVEF levels. In conclusion, serum GPBB, Mb, and BNP levels in combination might provide higher diagnostic accuracy in the early detection of AIC compared with other single indicators.

197. Markers of maternal cardiac dysfunction in pre-eclampsia and superimposed pre-eclampsia

Introduction Women who experience hypertensive disorders of pregnancy have an increased risk of developing cardiovascular disease in later life. The mechanism underlying this association unknown. Objectives To determine whether elevated glycogen phosphorylase isoenzyme B (GPBB) and/or brain natriuretic peptide (BNP) concentrations suggestive of cardiac dysfunction are observed in pre-eclampsia and superimposed pre-eclampsia (SPE). Method Four groups of women were selected from an existing cohort study: healthy controls (n = 21), pre-eclampsia (n = 19), pre-existing chronic hypertension (CHT) and/or chronic kidney disease (CKD) without (n = 20), or with SPE (n = 19). Plasma samples taken in the third trimester or at time of disease were assayed using Diagenics Dianeonatal® Glycogen phosphorylase Isoenzyme BB (GP-BB)-ELISA in vitro diagnostic device kits and Alere Triage © CardioRenal assays (BNP). Log transformed GPBB and BNP concentrations were compared using interval regression as ratios of the geometric means with 95% confidence intervals. Results No difference was observed in GPBB plasma concentrations between the control and pre-eclampsia groups (mean [95% C.I.]: 4.72 [2.49–8.94] ng/mL vs 4.98 [2.52–9.84] ng/mL; N = 40, p = 0.91), or between CHT and/or CKD and SPET groups (mean [95% C.I.]: 9.49 [4.93–18.25] ng/mL vs 10.24 [5.27–19.92] ng/mL; N = 39, p = 0.87). BNP plasma concentrations were significantly raised in the pre-eclampsia group compared to the control group (mean [95% C.I.]: 31.75 [19.21–52.49] pg/mL vs 11.31 [7.00–18.25] pg/mL; N = 40, p = 0.004), but did not reach statistical significance between the SPET and CHT and/or CKD groups (GM [95% C.I.]: 20.66 [12.40–34.44] pg/mL vs 16.06 [9.83–26.23] pg/mL; N = 39, p = 0.486). Discussion There was no difference in GPBB concentration between groups. BNP concentrations were elevated in cases of pre-eclampsia compared to controls. This suggests cardiac dysfunction at the time of pre-eclampsia but through a mechanism other than cardiac ischaemia, and little role for the use of GPBB as a biomarker in hypertensive disorders of pregnancy.

Glycogenolysis in Acquired Glioma Resistance to Temozolomide: A Role for the [Ca2+]i-dependent Activation of Na,K-ATPase/ERK1/2 Signaling.

Understanding the mechanistic basis for temozolomide (TMZ)-induced glioma resistance is an important obstacle in developing an effective form of chemotherapy for this type of tumor. Glycogenolysis is known to play an essential role in cellular proliferation and potassium homeostasis and involves the glycogen phosphorylase isoenzyme BB (GPBB). In this investigation, plasma GPBB was correlated with TMZ-resistance. Elevated plasma GPBB concentrations were found to be more frequent in a TMZ-resistant cohort of patients with poor survival rates. TMZ inhibits cell proliferation and induces TMZ resistance by upregulating the expression of O(6)-methylguanine-DNA methyltransferase (MGMT). This process requires glycogenolysis, which was confirmed herein by treatment with 1,4-dideoxy-1,4-imino-D-arabinitol hydrochloride, a glycogenolysis inhibitor and a special GPBB inhibitor. Acute TMZ treatment leads to upregulation of [Ca2+]i, extracellular-regulated kinase (ERK)1/2 phosphorylation, and chronic TMZ treatment leads to upregulation of the expression of Na,K-ATPase, ERK1/2, and MGMT protein. Upregulation was abolished for each of these by inhibitors of transient receptor potential channel 1 and the inositol trisphosphate receptor. L-channel [Ca2+]i inhibitors and RyR antagonists had no such effect. These results demonstrate that [Ca2+]i-dependent glycogenolysis participates in acquired glioma TMZ-resistance by upregulating MGMT via a Na,K-ATPase/ERK1/2 signaling pathway. GPBB and glycogenolysis may therefore represent novel therapeutic targets for overcoming TMZ-resistant gliomas.

Significance of heart-type fatty acid binding protein and brain glycogen phosphorylase isoenzyme type in septic myocardial injury

Objective To demonstrate the relevance of heart-type fatty acid binding protein(H-FABP) and brain glycogen phosphorylase isoenzyme type(GPBB) with myocardial injury in sepsis.To explore the effect of H-FABP and GPBB on the severity of disease and clinical prognosis. Methods A total of 40 cases of children with sepsis were selected in this study from January 1, 2017 to October 31, 2017.According to the illness severity, they were divided into sepsis group(n=15), severe sepsis group(n=13) and septic shock group(n=12), 19 cases of children with non-infectious diseases were selected as the control group for the same period.The levels of serum WBC, C-reactive protein, procalcitonin, cTnI, CK, CK-MB, CK-MB isoenzyme quality and NT-proBNP were collected within 24 hours of admission.The APECHEⅡ scores were calculated for each child.The peripheral blood of the patients within 24 hours after admission was used to determine the levels of serum H-FABP and GPBB by ELISA method.The differences of clinical indicators among the groups were analyzed.According to the survival of patients with sepsis, they were divided into 37 cases in the improved group and 3 cases in the death group.All patients with sepsis were divided into left ventricular ejection fraction(LVEF) normal group(n=26) and LVEF decreased group(n=14). According to whether the serum cTnI was elevated, all children with sepsis were divided into cTnI normal group (n=29) and cTnI increased group (n=11). The differences of H-FABP and GPBB levels were compared.According to the presence or absence of LVEF decline, the area under the ROC curve was used to evaluate the predictive power of each index for myocardial injury in sepsis.Based on the decrease of LVEF, the area under the ROC curve was used to evaluate the prediction of each index for myocardial injury in sepsis. Results There were significant differences in H-FABP and GPBB levels among the control group, sepsis group, severe sepsis group and the septic shock group (H=42.241, P 0.05), there was an elevated trend of H-FABP and GPBB in the death group.The levels of H-FABP (t=-3.770, P=0.001) and GPBB (Z=-2.113, P=0.033) were statistically significant in the LVEF normal group and the LVEF decreased group (LVEF≤60%). There were no significant differences in the levels of H-FABP and GPBB between the cTnI normal group and the cTnI increased group (P>0.05), but the cTnI increased group had an increasing trend.The area under the ROC curve in the diagnosis of myocardial injury in sepsis were H-FABP 0.821, NT-ProBNP 0.738, GPBB 0.661, CK 0.560, cTnI 0.512, in which the sensitivity(0.833) and specificity(0.786)of H-FABP were both higher. Conclusion The serum H-FABP and the GPBB levels can be used to monitor for myocardial damage, and it has a correlation with the severity of the disease and the prognosis.H-FABP has a significant advantage over traditional myocardial markers in sensitivity and specificity to determine the myocardial injury of sepsis. Key words: Sepsis; Myocardial injury; Cardiac markers; Heart-type fatty acid binding protein; Brain glycogen phosphorylase isoenzyme type

Heart-type fatty acid binding protein (H-FABP) as a biomarker for acute myocardial injury and long-term post-ischemic prognosis.

Acute myocardial infarction (AMI) is a life-threatening event. Even with timely treatment, acute ischemic myocardial injury and ensuing ischemia reperfusion injury (IRI) can still be difficult issues to tackle. Apart from radiological and other auxiliary examinations, laboratory tests of applicable cardiac biomarkers are also necessary for early diagnosis and close monitoring of this disorder. Heart-type fatty acid binding protein (H-FABP), which mainly exists inside cardiomyocytes, has recently emerged as a potentially promising biomarker for myocardial injury. In this review we discuss the sensitivity and specificity of H-FABP in the assessment of myocardial injury and IRI, especially in the early stage, and its long-term prognostic value in comparison with other commonly used cardiac biomarkers, including myoglobin (Mb), cardiac troponin I (cTnI), creatine kinase MB (CK-MB), C-reactive protein (CRP), glycogen phosphorylase isoenzyme BB (GPBB), and high-sensitivity cardiac troponin T (hs-cTnT). The potential and value of combined application of H-FABP with other biomarkers are also discussed. Finally, the prospect of H-FABP is summarized; several technical issues are discussed to facilitate wider application of H-FABP in clinical practice.

Heat shock protein 27 and glycogen phosphorylase isoenzyme BB as markers of myocardial stunning in male water polo players

Introduction: Sudden cardiac death has a tendency to increase among elite athletes. It has been reported that endurance exercise increased serum concentrations of cardiac biomarkers in elite athletes although it is unclear whether is clinically significant or is a part of the physiological response. Lately, the theory of myocardial stunning is attractive since there is no permanent cellular damage and is transient nature. This prompts us to evaluate the significance of Hsp27 and GP-BB as sensitive and specific biomarkers of myocardial stunning in elite male water polo players. Materials and Methods: A prospective and experimental study included 20 elite male water polo players, randomly divided into two groups that matched for age, length of active practicing water polo and level of physical stamina. Blood samples for testing were obtained at the following time points: baseline, 1, 30 and 60 min following exercise as well as for control group. Results: Endurance exercise has resulted in an increased serum concentration of Hsp27 at 50% after 1, 60% after 30 and 80% of water polo players after 60 min. Simultaneously, serum concentration of GPBB were increased in 40% of water polo players after 1 min as well as for 10% after 30 and 60 min. Further analysis has established significantly positive correlations among obtained serum concentration of Hsp27 and GP-BB at 1 (p<0.05) and 30 (p<0.01) min. Conclusion: Serum concentration of Hsp27 could be important indicator of the risk assessment and prevention of developing heart damage in water polo players or for athletes in general. Positive correlation between Hsp27 and GP-BB indicating the reversibility damages of structural and contractile proteins in myocardial cells. Further investigation is needed to investigate connection to oxidative stress as a significant part of metabolic exhaustion of myocardial cells.

Correlation of heart-type fatty acid-binding protein and glycogen phosphorylase enzyme BB in brain with septic myocardial injury

The incidence of sepsis is on the rise, and the mortality is also high.Myocardial injury caused by sepsis is one of the important causes of death.However, there is no clear and unified diagnostic criteria to sepsis complicated with myocardial injury.The clinical diagnostic criteria of myocardial injury is mainly based on cardiac ultrasound, myocardial markers and so on.But the measurement of ejection fraction is needed to consider the impact of preload and afterload of left ventricula, also the subjective level of operators.So cardiac markers play an important role in the detection of myocardial injury in sepsis and can reflect the severity of myocardial injury and sepsis, especially in the early diagnosis and prognosis.Heart-type fatty acid binding protein and brain glycogen phosphorylase isoenzyme type exhibit higher sensitivity, specificity and stability compared to other traditional cardiac markers in the clinical diagnosis of myocardial injury, which are worth to be studied and applied in the clinical diagnosis of myocardial injury. Key words: Sepsis; Myocardial injury; Cardiac markers; Heart-type fatty acid binding protein; Brain glycogen phosphorylase isoenzyme type

Difference in glycogen metabolism (glycogen synthesis and glycolysis) between normal and dysplastic/malignant oral epithelium

BackgroundThe purpose of this study was to investigate a difference in glycogen metabolism (glycogen synthesis and glycolysis) between the iodine stained (normal non-keartinized) and the unstained (dysplasctic/malignant) oral epithelium. MethodsTwenty-one frozen tissue samples of iodine-stained and unstained mucosal tissue were obtained from 21 OSCC patients. Serial frozen sections were cut and examined with the hematoxylin-eosin and periodic acid-Schiff methods and immunohistochemical (IHC) staining for Ki67, P53, molecules associated with glycogenesis (i.e., glycogen synthase (GS) and phospho-glycogen synthase (PGS)), and molecules associated with glycogenolysis (i.e., glycogen phosphorylase isoenzyme BB (GPBB) examine the glycogen metabolism in OSCC. Additionally, in vitro study, the expression levels of GS and GPBB in the cultured cells were analyzed by immunofluorescent staining, Western blot analysis, and the real-time quantitative polymerase chain reaction (PCR). ResultsThere was no significant difference in GS and PGS immunoactivity between iodine stained and unstained area. On the other hand, significantly greater GPBB immunoreactivity was observed in the basal and parabasal layers of iodine-unstained epithelium, where higher positivity for p53 and Ki67 was also showed. Additionally, western blot analysis, immunofluorescent staining, and real-time quantitative PCR revealed that the oral squamous cancer cells exhibited greater expression of GPBB than normal epithelial cells. ConclusionsThe results of this study showed that GPBB expression, which resulted in up-regulation of glycogenolysis, is enhanced in oral dysplastic/malignant epithelium compared with non-keartinized normal epithelium, in spite of the fact that glycogenesis continues in both of them. Premalignant and malignant epithelial cells consume greater quantities of energy due to their increased proliferation, and hence, exhaust their glycogen stores, which resulting in negative stain reaction with iodine solution.

Clinical effects of Ganglioside and fructose-1, 6-diphosphate on neonatal heart and brain injuries after Asphyxia.

Objective:To study the clinical effect of ganglioside (GM) and fructose-1, 6-diphosphate (FDP) on neonatal heart and brain injuries after asphyxia.Methods:Ninety-one neonates with asphyxia neonatal heart and brain injuries were randomly divided into an observation group and a control group. Both groups were given symptomatic treatment as soon as possible. On this basis, the observation group was given 200 mL of 5% glucose injection and 20 mg of GM and 250 mg/kg·d FDP by intravenous infusion. The above two drugs were given once a day for 14 days. The control group was given 20 mL of 5% glucose injection, 2 mL of cerebrolysin and 250 mg/kg·d FDP by intravenous infusion, once a day for 14 days. Both groups were administered on the first day after admission, and the course of treatment was 14 days. The treatment outcomes of the two groups were compared by detecting the levels of glycogen phosphorylase isoenzyme BB (GPBB), cTn-I and CK-MB, MRI results and Neonatal Behavioral Neurological Assessment (NBNA) scores before and after treatment.Results:The levels of GPBB, cTn-I and CK-MB in the observation group were significantly higher than those of normal neonates. After treatment, the levels of cTn-I and CK-MB in the observation group were closer to those of normal neonates compared with the control group, with significant differences (P<0.05). There was a significant difference in the brain MRI examination between the two groups (P<0.05). The NBNA scores of the two groups were significantly different before and after treatment (P<0.05). The total effective rate of the observation group was significantly higher than that of the control group (P<0.05).Conclusion:Neonatal heart and brain injuries after asphyxia can be well treated by combining GM with FDP.

Altered Maternal Plasma Glycogen Phosphorylase Isoenzyme BB as a Biomarker for Preeclampsia and Small for Gestational Age.

To investigate whether maternal plasma glycogen phosphorylase BB (GPBB) levels were altered in early pregnancy and/or at the time of diagnosis of disease in preeclampsia (term and preterm <37 weeks' gestation) or small for gestational age (SGA). We conducted 6 nested case-control studies within the Screening of Pregnancy Endpoint (SCOPE) Ireland cohort. Blood samples from women with preeclampsia or SGA were analyzed both from the time of disease presentation and at 15 and 20 weeks' gestation. These were compared with control samples obtained from SCOPE women with healthy uncomplicated pregnancies matched for age, ethnicity, parity, body mass index, and gestational age. Glycogen phosphorylase BB levels were measured using the Diacordon GPBB enzyme-linked immunosorbent assay (Diagenics, Germany). Glycogen phosphorylase BB levels were higher in women with preeclampsia compared with controls at the time of disease (term preeclampsia median [interquartile range (IQR)]: 22.2 [15.1-39.8] ng/mL vs 16.9 [10.4-19.1] ng/mL; P = .04; N = 14 and preterm preeclampsia median [IQR]: 23.1 [11.2-30.9] ng/mL vs 17.2 [9.8-19.1] ng/mL; P = .04; N = 11) and at 20 weeks' gestation (median [IQR]: 23.0 [15.6-31.4] ng/mL vs 17.0 [13.4-23.6] ng/mL; N = 39; P = .04). Glycogen phosphorylase BB levels were also significantly higher in women with SGA compared with normal controls at the time of disease detection (median [IQR]: 22.7 [12.6-25.5] ng/mL vs 17.0 [9.8-18.0] ng/mL; N = 23; P = .03) but significantly less than controls at 15 weeks' gestation prior to disease detection (median [IQR]: 16.0 [12.1-23.2] ng/mL vs 22.2 [17.0-28.9] ng/mL; N = 25; P = .02). Glycogen phosphorylase BB alone has modest predictive abilities for the development of preeclampsia or SGA. Further research may examine its use in combination with other markers.