The Indonesian Biomedical Journal

11-28

Authors: Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: Aging is an unavoidable part of life, defined by a gradual loss in tissue and organ function and an increasing chance of death. Current studies of aging connected the genetic and epigenetic changes to cause this process. CONTENT: When the aging-related epigenetic alterations is accumulated, it may result in irregulated gene expression, metabolic instability, stem cell senescence and exhaustion, and imbalance of tissue homeostasis, which all accelerate the aging process. Altered epigenetic gene regulatory mechanisms such as DNA methylation, histone modification and chromatin remodeling, and non-coding RNAs can induce aging process, thus manipulating these processes give a chance for the success of age-delaying interventions. SUMMARY: Given updated tools and technologies to investigate the epigenetic regulation affecting aging processes, new therapeutic strategies to delay this process can be developed to increase longevity and improve quality of life.

36-44

Authors: Mykyta Valilshchykov, Volodymyr Babalyan, Тetiana Markina, Marina Kumetchko, Liudmyla Boiko, Sergey Romaev

BACKGROUND: In patients with a fracture of the proximal femur and concomitant arterial hypertension, there is a disturbance of the reparative processes of bone tissue. This research aimed to study the regulation of the reparative processes of fractures of the proximal femur with intramedullary osteosynthesis during the correction of concomitant hypertension, which was examined based on some markers using the rat model. METHODS: The study involved healthy Wistar rats and spontaneously hypertensive rats (SHR). The subjects were then grouped into healthy rats without exposure (1.1) SHR without exposure (2.1), healthy rats with modeled fractures of the proximal femur (1.2), SHR with modeled fractures of the proximal femur (2.2), SHR underwent hypertension correction with enalapril in subgroups without fracture (2.3) and SHR underwent hypertension correction with enalapril in subgroups with fracture (2.4). The levels of interleukin (IL)-6, tumor necrosis factor alpha (TNF-a), IL-10, amino-terminal propeptide procollagen type III (PIIINP), glucose, uric acid, creatinine, urea, cholesterol, and albumin were determined in the blood serum of the animals. Femur preparations were examined after the removal of intramedullary fixation. RESULTS: Serum IL-6 level of animal in group 2.4 (2.297±0.361 pg/mL) were reduced compared to the corresponding indicators of rats in group 2.3 (4.054±0.491 pg/mL, p<0.05). Serum glucose and urea levels of animal in group 2.4 (3.951±0.156 mmol/L, 6.552±0.426 mmol/L, respectively) were significantly reduced in comparison with the group 2.3 (6.384±0.890 mmol/L, 10.369±0.888 mmol/L, respectively). The histological results indicated a positive effect of the drug enalapril on the healing of fractures of the proximal femur in animals with hypertension. CONCLUSION: Correction of arterial hypertension with enalapril in fractures of the proximal femur improves the reparative processes of bone tissue.

52-8

Authors: Dewi Wulandari, Alida Roswita Harahap, Suhendro Suhendro, R. Tedjo Sasmono, Aryati Aryati, Herdiman Theodorus Pohan, Iris Rengganis, Saptawati Bardosono

BACKGROUND: Dengue infection remains a major public health problem in Indonesia. Severe dengue associated with plasma leakage require hospitalization and potentially life threatening. However, the mechanism remains unclear, and the occurrence is unpredictable. The role of anti-endothelial antibody is predicted play an important role in the pathogenesis of plasma leakage, as severe dengue is more prevalent in secondary infection or post vaccinated individuals. METHODS: Serum samples from 127 single Dengue Virus (DENV) serotype infected subjects were obtained in day 2 of fever onset. Subjects were divided into plasma leakage and non-plasma leakage based on World Health Organization (WHO) criteria. Anti-endothelial antibody in patient sera were detected using western blot of Human Umbilical Vein Endothelial Cells (HUVEC). To confirm cross-reactivity, the sera was preabsorb with mix-DENV lysate. RESULTS: Three prominent bands were identified on western blot strips that inhibited by pre-absorption with DENV lysate. Plasma leakage patient expressed significantly more antibodies, with 51.7% of plasma leakage patients expressed at least two bands out of those three, compared to 18.5% of non-plasma leakage. CONCLUSION: Antibodies found in sera of dengue patients with plasma leakage cross-reacted with DENV proteins and endothelial proteins 37 kDa, 75 kDa, 120 kDa, and therefore may be involved in the pathogenesis of plasma leakage. Proteomic identification of those protein targets is needed and may be useful for vaccine studies and further development of predictor marker for plasma leakage in dengue.

66-73

Authors: Todung Silalahi, Idrus Alwi, Frans Suyatna, Katarina Dewi Sartika, Christopher Surya Suwita

BACKGROUND: Percutaneous coronary intervention (PCI) is the most common intervention for coronary artery disease (CAD) with very low complications. High oxidative stress post-PCI is associated with further atherosclerosis progression. Curcumin, extracted from a specific type of herbs, exhibits anti-oxidant properties by acting as hydrogen and electron donor for superoxide radicals. The aim of this study is to determine the effect of curcumin’s antioxidant properties in reducing oxidative stress of post-PCI in stable CAD. METHODS: This study was a double-blind parallel randomized controlled trial among 50 stable CAD patients undergoing PCI in Cipto Mangunkusumo General Hospital and Jakarta Heart Center. The subjects received either 45 mg/day curcumin or placebo 7 days pre-PCI until 48 hours post-PCI. Reduced oxidative stress markers (decreased MDA or increased GSH) were measured in 3 phases (7 days pre-PCI, 24 hours post-PCI, 48 hours post-PCI). RESULTS: Curcumin group showed increased MDA from baseline to 24 hours (Δ1=0.01 vs. 0.03; p=0.3) and decreased MDA from baseline to 48 hours (Δ2=-0.06 vs. 0.03; p=0.9). While, curcumin group showed decreased GSH from baseline to 24 hours (Δ1=-49.7% vs. 12.2%; p=0.4) and from baseline to 48 hours (Δ2=-19.09% vs. 11.4%; p=0.6). However, no significant changes were found in malondialdehide (MDA) and glutathione (GSH) level after the intervention. CONCLUSION: The 45 mg/day curcumin supplementation from 7 days pre-PCI until 48 hours post-PCI had no significant antioxidant effect in stable CAD post-PCI.

84-90

Authors: Kusmardi Kusmardi, Bagas Ariffandi, Nadar Sukri Lubis, Tri Wahyuni Lestari, Putri Reno Intan, Alfred Pakpahan

BACKGROUND: Malaria remains a global health concern and an endemic disease in Indonesia. Sambiloto (Andrographis paniculata) and spirulina (Spirulina platensis) are two potential antimalarial agents which act as antioxidants and antiinflammatories that can suppress morbidities during chronic inflammation in malaria, such as proliferation in the colon. This study aims to investigate the effects of A. paniculata extract and S. platensis administration on Ki-67 expression in medial colon epithelial cells of Plasmodium berghei-infected mice measured by H-score. METHODS: Thirty P. berghei-infected male Swiss-Webster mice were divided into five groups: negative controls (carboxymethyl cellulose/CMC); positive controls (dihydroartemisinin-piperaquine/DHP); A. paniculata extract alone (AP); A. paniculata extract in combination with S. platensis extract (AP+ES); and with S. platensis powder (AP+PS). All mice were infected with P. berghei on day 0. The treatment for each group were given 3 days before infection (D-3) until the day of infection (D0) for 28 days after infection. Colon tissues were processed with immunohistochemistry to detect Ki-67. RESULTS: A difference in Ki-67 expression was observed among the groups (p<0.01). The mean H-score for the CMC control group is 135.503±6.723. The lowest level of Ki-67 expression was observed in the AP+PS group (H-score= 110.941±7.079). AP group did not show a significant difference from the CMC group (p=0.514) and neither did the AP+ES group (p=0.234). CONCLUSION: In conclusion, administration of A. paniculata extract and S. platensis powder lowers Ki-67 expression in medial colon epithelial cells of P. berghei-infected mice.

98-103

Authors: Mabruratussania Maherdika, Indranila Kustarini Samsuria, Meita Hendrianingtyas, Nyoman Suci Widyastiti, Muji Rahayu

BACKGROUND: Inflammation occurs in chronic diseases such as type 2 diabetes mellitus (DM). Insulin resistance and inflammation in type 2 DM with obesity can increase interleukin (IL)-6, causing an increase in hepcidin synthesis in the liver. Increased inflammation can exacerbate the course of type 2 DM. This study aims to prove that there are differences in the levels of hepcidin and IL-6 between obese and non-obese type 2 DM. METHODS: This cross-sectional study was conducted on 61 patients with type 2 DM, consist of 22 male and 39 female with an age of more than 40 years. Type 2 DM subjects were obtained from a doctor's diagnosis and were divided into obese and non-obese groups based on body mass index (BMI). Hepcidin and IL-6 levels were examined using the Enzyme-Linked Immunosorbent Assay (ELISA) principle. The data were analyzed using an independent t-test and Mann-Whitney test. RESULTS: The mean level of hepcidin in the obese with type 2 DM group was 25.32±11.54 ng/mL, and non-obese was 11.94±5.31 ng/mL. The median level of IL-6 in the obese with type 2 DM group was 11.9 (5-61) pg/mL, and non-obese 4.8 (1.5-9.8) pg/mL. There was a significant difference in hepcidin and IL-6 levels between the obese and non-obese groups (p=0.000). CONCLUSION: Hepcidin and IL-6 levels in the obese group with type 2 DM were higher than non-obese group.