Effect of remote ischemic postconditioning on left ventricular ejection fraction in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: Ischemic conditioning may help patients with ST-segment elevation myocardial infarction (STEMI) to limit ventricular remodeling. OBJECTIVES: To investigate the effect of remote ischemic postconditioning (RIPC) on left ventricular function during primary percutaneous coronary intervention (PPCI) in patients with STEMI. MATERIAL AND METHODS: Pre- and post-test intervention study with a total of 60 STEMI patients. Patients were divided in two groups: with and without RIPC. RESULTS: During the 6-month follow-up, a significant difference in left ventricular ejection fraction was observed in patients who underwent PPCI, which was higher in the group with RIPC in comparison with the group without RIPC: 1.0% (-1.0 to 4.3) vs. -1.0% (-4.0 to 1.3), p = 0.033. In addition, at 6-month measurement, left ventricular end-systolic volume in patients without RIPC was higher in comparison with their counterparts: 79.3 ± 30.5 mL vs. 64.4 ± 21.4 mL, p = 0.032. CONCLUSIONS: RIPC shows favorable effects on left ventricular function and, therefore, in the future, it could be a potential cardioprotective strategy against ischemia-reperfusion injury in STEMI patients.

ANTECEDENTES: En los pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST), el acondicionamiento isquémico puede ayudar a limitar la remodelación ventricular. OBJETIVOS: Investigar el efecto del posacondicionamiento isquémico remoto (PAIR) en la función del ventrículo izquierdo durante la intervención coronaria percutánea primaria (ICPP) en pacientes con IAMCEST. MATERIAL Y MÉTODOS: Estudio de intervención pre y posprueba con un total de 60 pacientes con IAMCEST. Los pacientes fueron divididos en dos grupos: con y sin PAIR. RESULTADOS: En el seguimiento de seis meses se observó una diferencia significativa en la fracción de eyección del ventrículo izquierdo en pacientes con ICPP, la cual fue mayor en el grupo con PAIR en comparación con el grupo sin PAIR: 1.0 (−1.0 a 4.3) versus −1.0 (−4.0 a ­1.3), p = 0.033. En la medición de seis meses, el volumen sistólico final del ventrículo izquierdo en los pacientes sin PAIR fue mayor en comparación con el grupo homólogo: 79.3 ± 30.5 mL versus 64.4 ± 21.4 mL, p = 0.032. CONCLUSIONES: PAIR muestra efectos favorables en la función ventricular izquierda y, por lo tanto, en el futuro podría ser una estrategia cardioprotectora potencial contra la lesión por isquemia-reperfusión en pacientes con IAMCEST.

Efecto del posacondicionamiento isquémico remoto sobre la fracción de eyección del ventrículo izquierdo en pacientes con infarto de miocardio con elevación del segmento ST sometidos a intervención coronaria percutánea primaria / Effect of remote ischemic postconditioning on left ventricular ejection fraction in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

Resumen Antecedentes: En los pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST), el acondicionamiento isquémico puede ayudar a limitar la remodelación ventricular. Objetivos: Investigar el efecto del posacondicionamiento isquémico remoto (PAIR) en la función del ventrículo izquierdo durante la intervención coronaria percutánea primaria (ICPP) en pacientes con IAMCEST. Material y métodos: Estudio de intervención pre y posprueba con un total de 60 pacientes con IAMCEST. Los pacientes fueron divididos en dos grupos: con y sin PAIR. Resultados: En el seguimiento de seis meses se observó una diferencia significativa en la fracción de eyección del ventrículo izquierdo en pacientes con ICPP, la cual fue mayor en el grupo con PAIR en comparación con el grupo sin PAIR: 1.0 (−1.0 a 4.3) versus −1.0 (−4.0 a –1.3), p = 0.033. En la medición de seis meses, el volumen sistólico final del ventrículo izquierdo en los pacientes sin PAIR fue mayor en comparación con el grupo homólogo: 79.3 ± 30.5 mL versus 64.4 ± 21.4 mL, p = 0.032. Conclusiones: PAIR muestra efectos favorables en la función ventricular izquierda y, por lo tanto, en el futuro podría ser una estrategia cardioprotectora potencial contra la lesión por isquemia-reperfusión en pacientes con IAMCEST.

Abstract Background: Ischemic conditioning may help patients with ST-segment elevation myocardial infarction (STEMI) to limit ventricular remodeling. Objectives: To investigate the effect of remote ischemic postconditioning (RIPC) on left ventricular function during primary percutaneous coronary intervention (PPCI) in patients with STEMI. Material and methods: Pre- and post-test intervention study with a total of 60 STEMI patients. Patients were divided in two groups: with and without RIPC. Results: At 6-month follow-up evaluation, a significant difference in left ventricular ejection fraction was observed in patients who underwent PPCI, which was higher in the group with RIPC in comparison with the group without RIPC: 1.0 (−1.0 to 4.3) vs. −1.0 (−4.0 to –1.3), p = 0.033. In addition, at 6-month measurement, left ventricular end-systolic volume in patients without RIPC: was higher in comparison with their counterparts: 79.3 ± 30.5 mL versus 64.4 ± 21.4 mL, p = 0.032. Conclusions: RIPC shows favorable effects on left ventricular function and, therefore, in the future, it could be a potential cardioprotective strategy against ischemia-reperfusion injury in STEMI patients.

Non-monotonic dose-response of di-(2-ethylhexyl) phthalate isolated from Penicillium citrinum XT6 on adipogenesis and expression of PPARγ and GLUT4 in 3T3-L1 adipocytes.

OBJECTIVES: Adipogenesis is the fat cell formation process regulated by peroxisome proliferator-activated receptors (PPARγ). The insulin-responsive glucose transporter 4 (GLUT4) has a major role in glucose uptake and metabolism in insulin target tissues (i.e., adipose and muscle cells). The interplay between PPARγ and GLUT4 is essential for proper glucose homeostasis. This study aimed to isolate, elucidate, and investigate the effect of an isolated compound from Penicillium citrinum XT6 on adipogenesis, PPARγ, and GLUT4 expression in 3T3-L1 adipocytes. METHODS: The isolated compound was determined by analyzing spectroscopic data (LC-MS, FT-IR, Spectrophotometry UV-Vis, and NMR). The adipogenesis activity of the isolated compound in 3T3-L1 cells was determined by the Oil Red O staining method. RT-PCR was used to analyze the gene expression of PPARγ and GLUT4. RESULTS: Di-(2-ethylhexyl)-phthalate (DEHP) was the isolated compound from P.citrinum XT6. The results revealed adipogenesis stimulation and inhibition, as well as PPARγ and GLUT4 expressions. CONCLUSIONS: DEHP showed a non-monotonic dose-response (NMDR) effect on adipogenesis and PPARγ and GLUT4 expression. It is the first study that reveals DEHP's NMDR effects on lipid and glucose metabolism in adipocytes.

The RYR3 gene is involved in Wharton's jelly derived mesenchymal stem cell treatment of Alzheimer's disease in rats.

Introduction: Our study aims to observe the effect of mesenchymal stem cells (MSCs) in lowering amyloid accumulation and ryanodine receptor 3 (RYR3) gene expression, further improving cognitive dysfunction in Alzheimer's disease (AD). Methods: Twenty male adult Wistar rats were randomly distributed into three groups of animals (n = 5). The AlCl3 group was given 300 mg/kg body weight (BW) of AlCl3 intraperitoneally for 5 days, further the MSC injection, and their effect after 30 days was observed. Results: MSCs improved amyloid accumulation and Y-maze scores, and expression of the RYR3 gene decreased compared to the control group. Conclusions: MSCs improved amyloid accumulation, Y-maze scores, and RYR3 expression in the AD animal model.

The Role of High Sensitivity C-reactive Protein to Predict Delirium Persistence in Elderly Patients with Pneumonia: A Prospective Cohort Study.

BACKGROUND: Delirium is a disorder of acute full attention, and cognitive function commonly occurs at elderly which  can prolong hospitalization, dependence rate, morbidity, and mortality, with pneumonia infection as one of its risk factors. Several markers have been studied for delirium, but relationship between delirium severity and persistence remains unclear. This study aimed to examine the role of hs-CRP, pNF-H, S100B, and NLR to predict delirium persistence.  Methods: A prospective  cohort study was  conducted among 80 subjects who were admitted to the internal ward in dr. M. Djamil Hospital in Padang. Subjects were grouped based on severity of delirium using the Memorial Delirium Assessment Scale and  followed up until discharged to determine delirium persistence event. RESULTS: Mean age of subjects is 70.7±7.4 years, 39 (48.8%) male and 41 (51.2%) female,consisting of 29 mild, 26 moderate, and 25 severe delirium. Levels of hs-CRP in mild, moderate, and severe delirium are 13.36±0.79, 13.56±0.78, and 13.88±0.59 mg/L (p=0.038), respectively. Median NLR values for mild, moderate, severe delirium were 6.80 (1.00-31.00), 9.50 (3.60-46.00), and 11.90 (2.80-46.50) (p=0.026). Cut off value hs-CRP 13.61 mg/L has significant difference for delirium persistence event (OR 2,54; 95% CI 1,01-6,39). Median levels of pNF-H and S100B are not significant in different delirium severity, regardless of non-persistent or persistent. CONCLUSION:   Hs-CRP levels exceeding 13.61 can predict risk of persistent delirium, but not with levels pNF-H, S100B, and NLR.

Ocimum basilicum alleviates blood glucose, lipid profile and iNOS in diabetes gestational rat model.

OBJECTIVES: Gestational diabetes (GDM) complications affect maternal and fetus in utero. GDM's vascular dysfunction showed inducible nitric oxide synthase (iNOS) alteration and was linked to the higher production of nitrogen species, leading to diabetic embryopathy. Ocimum basilicum (O. basilicum) has been reported for its anti-inflammatory and anti-diabetic effects. Thus, the present study investigates the anti-diabetic effect, lipid-lowering effect, and iNOS expression in GDM animal models treated with O. basilicum extract. EXPERIMENTAL PROCEDURES: Four groups of pregnant rats consist of control and GDM groups. One GDM group was set for control positive. Two GDM groups were treated with O. basilicum extract in two doses (100 and 200 mg/kg BW) for 14 days. Blood glucose of all groups was observed at 72 h after STZ injection and 14 days after administration of O. basilicum extract. Lipid profile and iNOS expression using real-time PCR were measured afterward. RESULTS: O. basilicum extract lowered blood glucose levels in both doses, from 262.60 mg/dL±6.89-136.80 mg/dL ± 15.6 mg/dL and 113.20 mg/dL±5.25 mg/dL. Total cholesterol, LDL and triglyceride showed a reduction, especially in 200 mg/kg BW dose extract from 122.37 mg/dL ± 14.84 mg/dL, 69.75 mg/dL±3.78 mg/dL and 137.51 mg/dL ± 8.12-74.64 mg/dL±8.71 mg/dL, 40.26 mg/dL±3.31 mg/dL and 87.57 mg/dL±6.29 mg/dL, respectively. iNOS expression downregulated in both doses, from 2.17±0.39 to 0.94±0.3 and 0.41±0.08. CONCLUSIONS: This study showed that O. basilicum extract has a potential therapeutic activity in lowering blood glucose, improved lipid profile, and downregulating iNOS in GDM.

SCUBE2, vascular endothelium, and vascular complications: A systematic review.

The vascular endothelium plays a vital role in regulating normal vascular function. Endothelial lining maintains the balance of thrombolytic and fibrinolytic microenvironment in the vasculature. Alterations of vascular endothelium referred to as endothelial dysfunction, caused the pathological changes in vessel wall such activation of proinflammatory and procoagulatory that initiate atherosclerosis. The concept that endothelial dysfunction plays a critical role in the initiation of atherosclerosis due to vascular inflammation gained tremendous attention. Diabetes mellitus is a metabolic-related disease that caused high mortality and morbidity, leading to its cardiovascular complication over the past decade. Atherosclerosis is the leading cardiovascular complication in diabetes mellitus. Despite metabolic and glycemic control, atherosclerotic plaque progression remains an enormous problem in diabetes mellitus complications. Thus, new inroads therapeutic approach in preventing complications that induced inflammation in endothelial cells could help prevent the disease progression. Signal peptide-CUB-EGF like domain-containing protein 2 (SCUBE2) expressed in vascular endothelium and reported to involve in inflammation. A recent study reported an increased SCUBE2 expression in diabetes mellitus and correlated with high expression of endothelin-1 (ET-1), a proinflammatory endothelial cell-derived peptide. Moreover, this gene showed to increase during atherosclerosis development. The present systematic review will summarize the involvement of SCUBE2 in vascular endothelium function changes and vascular complication, particularly in diabetes mellitus and atherosclerosis.

Upregulation of SCUBE2 expression in dyslipidemic type 2 diabetes mellitus is associated with endothelin-1.

Type 2 diabetes mellitus (T2DM) is a major health problem for morbidity and mortality world-wide due to diabetic vascular complication. Following T2DM, dyslipidemia is known well for the main reason of vascular complication leading to atherosclerosis and impaired life expectancy in diabetes. Thus, a new prediction marker in T2DM could help prevent the progression disease despite of metabolic control. Signal peptide-CUB-EGF like containing protein 2 (SCUBE2), has been detected in vascular endothelium and was affected by cytokines. Recently, SCUBE2 was reported to increase in atherosclerotic human coronary artery, involving vascular smooth muscle cells (VSMCs) and macrophages. The aims of this study were to examine the expression level of SCUBE2 in T2DM patients with dyslipidemia and its correlation with endothelial dysfunction marker, endothelin-1 (ET-1) in this group. This study design was cross sectional control study, recruited 28 patients diagnosed as T2DM who were found with dyslipidemia and 15 healthy control subjects. Our results showed that T2DM patients showed higher LDL cholesterol, triglycerides, and ET-1 expression level compared to healthy subjects. Further, we found that SCUBE2 had strong correlation with ET-1 in these dyslipidemic T2DM patients. In conclusion, our study confirmed first that SCUBE2 was upregulated in T2DM with dyslipidemia. Moreover, Pearson correlation analysis of ET-1 and SCUBE2 in this group showed high correlation r = 0.797, P < 0.001, suggesting that SCUBE2 may plausible target in vascular function changes in dyslipidemic T2DM. Improving our exploration of these findings may lead to uncover SCUBE2 involvement in diabetic vascular complication in T2DM.

Upregulation of SCUBE1 in Dengue Virus Infection.

BACKGROUND: Dengue is a major communicable disease in tropical areas, with an increasing prevalence every year. Thrombocytopenia is one of the commonly used laboratory parameters for predicting the severity of the disease. It is detected on day 6 or day 7 after the febrile stage, and its presence indicates that the disease has become potentially fatal. Therefore, it is necessary to identify a marker for the early recognition of dengue virus infection during the febrile stage before the detection of thrombocytopenia on day 6 to prevent severe disease outcomes. Signal peptide-CUB- (complement C1r/C1s)-EGF (epidermal growth factor)-like domain-containing protein 1 (SCUBE1) is secreted in activated platelets under inflammatory conditions and enhances platelet-platelet adhesion and agglutination. This gene was first identified in human vascular endothelium, but its biological role in platelets remains unknown. AIM: This study aims to identify SCUBE1 expression during the febrile stage of dengue virus infection and examine the correlation of its expression with thrombocytopenia occurrence on day 6. MATERIAL AND METHODS: Blood samples were collected from 17 patients infected with dengue virus on day-3 fever and from 16 healthy controls who met the inclusion and exclusion criteria for dengue virus infection according to the World Health Organization (WHO) classification for dengue virus infection. All samples were subjected to SCUBE1 gene analysis using real-time reverse transcription quantitative PCR (RT-PCR). RESULTS: The results showed that upregulation of SCUBE1 gene in infected patients (8.9 ± 3.1-fold) compared to that in healthy controls, indicating SCUBE1 involvement in dengue virus infection. Furthermore, we analysed the laboratory parameters of infected patients on day 3 and day 6, when thrombocytopenia is usually detected. Platelet count was found to be significantly decreased from day 3 until day 6 in the infected patients. Unfortunately, our results showed no correlation between SCUBE1 expression in the febrile stage and the occurrence of thrombocytopenia on day 6. CONCLUSION: The conclusion of this study is SCUBE1 might play a role in dengue virus infection but does not correlate with thrombocytopenia on day-6 fever.

Localization and characterization of a novel secreted protein, SCUBE2, in the development and progression of atherosclerosis.

Inhibition of atherosclerosis progression has long been the subject of intensive pathophysiologic investigations. The identification of a novel target molecule to redeem the cellular processes remains a major challenge in cardiology. Signal peptide CUB domain EGF-like repeat protein (SCUBE) family has been detected on human tissues and cultured cells. Two members of the SCUBE family, SCUBE1 and SCUBE3 are reported to play a role in cardiovascular diseases. The other member, SCUBE2 has been reported to mediate Hedgehog (Hh) protein signaling and is expressed in major blood vessels during mouse embryogenesis. However its involvement in cardiovascular diseases is not known yet. The aim of this study was to investigate SCUBE2 expression and localization in diffuse intimal thickening (DIT), an early event of atherosclerosis and in advanced lesion of atherosclerotic plaque. Carotid artery ligation in C57BL/6J mice was performed to induce intimal thickening, mimicking DIT in human. After 2 weeks of ligation, mRNA level of SCUBE2 increased significantly, while in LDLr-/- mice fed with high fat diet, a human atherosclerosis model, mRNA level of SCUBE2 expression markedly increased 8 weeks after start of the high fat diet. Our findings were confirmed by the observation of SCUBE2 expression in human coronary artery with DIT and advanced lesion of atherosclerotic plaque. Previous investigations described that SCUBE2 mediates Hh signaling pathway. We have observed that SCUBE2 expression is associated with Sonic Hedgehog (Shh) and its receptor, Patched (Ptc), both in DIT and advanced plaque lesion. Our results suggested that SCUBE2 is a new target molecule in atherosclerosis and might play an important role in atherosclerotic plaque progression via Hh signal transduction.