Proprotein convertase subtilisin/kexin type 9 (PCSK9) as a marker of coronary lesion severity in stable coronary artery disease (CAD) patients.

Coronary artery disease (CAD) remains a significant global health concern with considerable high morbidity and mortality and its development is influenced by various genetic and environmental factors. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a vital regulator of low-density lipoprotein receptor (LDLR) metabolism, directly impacting serum cholesterol levels. However, its role in development of CAD is not fully understood. The aim of this study was to assess the association between the level of PCSK9 and coronary lesion severity in patients with CAD. A case-control study using consecutive sampling was conducted among CAD patients at H. Adam Malik General Hospital and Murni Teguh Memorial Hospital, Medan, Indonesia. A total of 200 CAD patients were divided into two groups based on the SYNTAX score: control (score ≤22, n=100) and case (score >22, n=100). Plasma PCSK9 levels were measured from venous blood using quantitative sandwich enzyme immunoassay. The Chi-squared test was used to analyze the data. Our data suggested that PCSK9 level was associated with coronary lesion severity (p<0.001) of which high PCSK9 level was associated with severe coronary lesion. We also found that hypertension (p<0.001), smoking (p=0.072), diabetes (p<0.001), dyslipidemia (p<0.001), obesity (p=0.023), and family history (p=0.001) were associated with lesion severity. Using the receiver operating characteristic (ROC) curve analysis, the cut-off 70.35 ng/mL of PCSK9 had sensitivity 75% and specificity 78% to predict severe coronary lesion. This study highlights that PCSK9 level has moderate sensitivity and specificity to predict the coronary lesion severity among CAD patients.

Anti-fibrotic effect of intravenous umbilical cord-derived mesenchymal stem cells (UC-MSCs) injection in experimental rats induced liver fibrosis.

Aim To investigate the effect of umbilical cord-derived mesenchymal stem cells (UC-MSCs) administration among liver fibrosis experimental rat model via the regulation of angiotensin II type 1 receptor (AT1R) and platelet-derived growth factor-ß (PDGF-ß) due to their therapeutic potential to replace liver transplantation for advanced liver fibrosis. Yet the mechanism of action has been questionably associated with UC-MSCs fibrosis regression properties. Methods Sprague-Dawley (SD) rats (n=18) were separated into three groups (control, untreated liver fibrosis, and UC-MSCs treated group). Serum PDGF-ß level was determined by enzymelinked immunosorbent assay (ELISA) following 14 days of UCMSCs injection. Meanwhile, AT1R expression was interpreted based on immunoreactive score (IRS) stained using polyclonal antibody and liver fibrosis stained with hematoxylin & eosin was graded using the METAVIR score. Results UC-MSCs were isolated successfully from rat umbilical cord. Liver fibrosis was observed following 14 weeks of CCl4 injection concurrent with higher serum level of PDGF-ß, but the UC-MSCs-treated group had lower level (980.08 ±289.41 and 606.42±109.85 for untreated liver fibrosis and UC-MSCs treated group, respectively; p=0.004). There was also a high expression of AT1R among untreated liver fibrosis group, as well as highgrade liver fibrosis versus localized fibrosis and low level of AT1R expression among UC-MSCs treated-group (p=0.001). Conclusion UC-MSCs administration could ameliorate liver fibrosis by reducing the AT1R expression and PDGF-ß serum levels, and intervention through this signaling pathway could be alternative evidence for the causative of positive outcome.

Intravenous Umbilical Cord-derived Mesenchymal Stem Cells Transplantation Regulates Hyaluronic Acid and Interleukin-10 Secretion Producing Low-grade Liver Fibrosis in Experimental Rat.

INTRODUCTION: Immunomodulation properties of mesenchymal stem cells have attracted tremendous attention that eventually could regress liver fibrosis process. AIM: The study aims to demonstrate the immunomodulation activities of Umbilical cord-derived Mesenchymal stem cells (UC-MSCs) affecting interleukin-10 (IL-10) and hyaluronic acid (HA) secretion post intraperitoneal injection of CCl4, potent hepatotoxin, induced liver fibrosis among experimental rats. METHODS: There were 18 Sprague-Dawley (SD) rats divided into three treatment groups (G1 sham group, G2 untreated liver fibrosis group, and G3 UC-MSCs treated-group) and isolated in Stem Cell and Cancer Research Facility, Semarang, Indonesia. Blood examination was conducted after 3 and 14 days of UC-MSCs transplantation using sandwich based ELISA followed by the histopathological analysis of rat liver tissue. ANOVA and posthoc LSD tests were determined the significance against all groups based on their quantitative measurement. RESULTS: UC-MSCs have been successfully extracted and isolated as well as positive with osteogenic differentiation (Alizarin dye). In further analysis, there were significant mean differences among all groups through the ANOVA test, both IL-10 and HA secretion, concurrent with low-grade liver fibrosis in G3. IL-10 elevates during the early phase of UC-MSCs transplantation, and HA significantly reduced on the 14th day of transplantation, it characterizes the liver fibrosis that has been attenuated. CONCLUSION: The transplantation of UC-MSCs has given an opportunity for the treatment of a wide range of chronic liver diseases through the immunomodulation properties via its paracrine effects that regulate specific cytokine to suppress fibrosis development.

Serum Ferritin Levels: A Potential Biomarker to Represent Child-Turcotte-Pugh Score among Decompensated Liver Cirrhosis Patients.

BACKGROUND: Liver cirrhosis and the child-Turcotte-Pugh (CTP) score are inseparable entities in liver disease. CTP score is largely known as the mortality and prognosis predictor. Nevertheless, ferritin emerges as a simple biomarker related to prognosis. The study aimed to determine whether there was a significant correlation between serum ferritin levels and CTP score. METHODS: The study analysed 54 decompensated liver cirrhotic patients including 17 females and 37 males between May 2016 and May 2017 at the Haji Adam Malik General Hospital, Medan, Indonesia. Ferritin levels were, then, divided into trichotomous cut-off value (< 200 ng/mL, n = 22; 200-400 ng/mL, n = 5; and > 400 ng/mL, n = 27). Data was analysed using SPSS version 12.0 (continuous variables were assessed by the Kruskal-Wallis test and Chi-square test was used for categorical variables). In addition, Spearman correlation test was used to determine any significant correlation between ferritin levels and CTP score. RESULTS: Based on data analysis, gender and CTP score were related to higher ferritin levels (P = 0.002 and P = 0.018, respectively). Furthermore, a significant correlation between serum ferritin levels and CTP score was obtained in to moderate degree (P = 0.000; r = 0.487). CONCLUSIONS: There might be a significant role of serum ferritin levels in predicting mortality and prognosis among decompensated liver cirrhosis patients but it still needs further attention.

Serum VEGF Levels in Helicobacter pylori Infection and Correlation with Helicobacter pylori cagA and vacA Genes.

BACKGROUND: Helicobacter pylori vacA and cagA genes are associated with higher virulence. Vascular Endothelial Growth Factor (VEGF) is one important marker for neo-angiogenesis. AIM: The purpose of this study was to investigate the relationship between VEGF serum levels with cagA and vacA genes in H. pylori infection. METHODS: A cross-sectional study was done on eighty patients that consecutive admitted to endoscopy unit. The diagnosis of H. pylori infection was based on rapid urease test. Serum samples were obtained to determine circulating VEGF level. Polymerase chain reaction was done to examine H. pylori vacA and cagA genes. Data analysis were carried-out using SPSS version 22. RESULTS: A total of 80 patients were examined. There were 45 (56.3%) patients infected with Helicobacter pylori. There were 33 (73.3%) patients with H. pylori cagA positive. Serum VEGF levels in patients with the H. pylori positive were significantly higher compared to the patients that have no H. pylori. Serum levels of VEGF were significantly higher in cagA positive than negative. CONCLUSION: Serum VEGF level is correlated with H. pylori infection and its virulence status. The more virulence of H. pylori, cagA gene, the higher serum VEGF levels were found.